Please Scroll Down to See Forums Below
Why the AMES test does not say DNP is safe
- Thread starter sk*
- Start date
All,
Ive heard something that some people are purporting that if a compound passes the AMES test, than it cannot or is likely NOT to cause cancer.
This is scientifically unsound ... and here is why.
The AMES test IS designed to find mutagens ... well specifically ones that cause frameshift mutations, let me explain.
in the AMES test, a bacteria has a mutation in any one of several metabolic pathways. In this sense, it cannot grow on what is called "minimal media" -- that is -- It can't grow with just food alone, it needs some help. Sometimes these mutations destroy its ability to synthesize a certain amino acid ... proline for example. Since the bacteria cannot make proline, it cannot grow. The media it grows in (its food) needs to have proline added to it for the bacteria to grow. No proline, no growth.
These bacteria usually have a nucleotide--a DNA base inserted into their DNA so the transcript made from the DNA is faulty MRNA...the mRNA codes for a protein that is "out of frame" and basically the result is a mutant, truncated protein. It is nonfunctional. This protein is usually an enzyme that is involved somewhere in a metabolic pathway as described above. This enzyme must be ESSENTIAL -- that is, without the bacteria cannot grow on MINIMAL MEDIA.
The AMES test take sthese bacteria in culture and adds to it YFC (your favorite compound). YFC can be DNP in this case. Two plates are setup. One has the bacteria plated on it, and YFC added to it. The second has YFC, the bacteria and HUMAN LIVER EXTRACT. The idea with the human liver extract is that most MUTAGENS (ie CARCINOGENS) are not inherently mutagenic. They require activation by human liver enzymes to make them toxic. Basically, your liver enzymes want to make compounds less toxic ... hence it tries to "detoxify" 17-aa when you take these; however, often they end up "activating" certain compounds and making them mutagenic when they initially were not. One example is benzene ... its not itself mutagenic, but when acted upon by liver enzymes, it will kick your ass.
They incubate these plates and wait to see what happens. Basically, they are waiting to see if YFC causes bacterial growth ... how does this happen you say? THE BACTERIA ARE MUTATED AND SHOULD NOT GROW!!!
If YFC with the liver extract is mutagenic ... it will cause a REVERSE mutation in the bacteria, restoring their ability to grown on MINIMAL MEDIA. The idea is translatable to people. In general, since you are healthy and have few mutations, the idea is that YFC compound tested, if it causes REVERSE mutations in bacteria, it will cause FORWARD mutations in you. And hence, it will kick YOUR ass.
However, the AMES test is old and has several inherent limitations. Here is why its NOT a good test for DNP.
a) The AMES test is only designed to Identify that a substance is a carcinogen, not establish that a compound is NOT carcinogenic. Proving a negative response is VERY difficult in science. A good analogy for this is the Roswell saying "absence of evidence is not evidence of absence." ...
b) DNP acts directly by blowing up the proton gradient established in the mitochondria. This really isnt all that important except to understand that it acts in mitochondria. however, you need to know BACTERIA DONT HAVE MITOCHRONDRIA! So how can it cause mutations in bacteria when they dont have the target of the compound?
Its well established that DNP dramatically increases the oxidative load on cells. IT is well established that oxidative stress correlates to an increased risk for carcinogenesis. I therefore conclude nothing shows DNP is safe AT ALL, and should be regarded with EXTREME CAUTION.
NFG
Ive heard something that some people are purporting that if a compound passes the AMES test, than it cannot or is likely NOT to cause cancer.
This is scientifically unsound ... and here is why.
The AMES test IS designed to find mutagens ... well specifically ones that cause frameshift mutations, let me explain.
in the AMES test, a bacteria has a mutation in any one of several metabolic pathways. In this sense, it cannot grow on what is called "minimal media" -- that is -- It can't grow with just food alone, it needs some help. Sometimes these mutations destroy its ability to synthesize a certain amino acid ... proline for example. Since the bacteria cannot make proline, it cannot grow. The media it grows in (its food) needs to have proline added to it for the bacteria to grow. No proline, no growth.
These bacteria usually have a nucleotide--a DNA base inserted into their DNA so the transcript made from the DNA is faulty MRNA...the mRNA codes for a protein that is "out of frame" and basically the result is a mutant, truncated protein. It is nonfunctional. This protein is usually an enzyme that is involved somewhere in a metabolic pathway as described above. This enzyme must be ESSENTIAL -- that is, without the bacteria cannot grow on MINIMAL MEDIA.
The AMES test take sthese bacteria in culture and adds to it YFC (your favorite compound). YFC can be DNP in this case. Two plates are setup. One has the bacteria plated on it, and YFC added to it. The second has YFC, the bacteria and HUMAN LIVER EXTRACT. The idea with the human liver extract is that most MUTAGENS (ie CARCINOGENS) are not inherently mutagenic. They require activation by human liver enzymes to make them toxic. Basically, your liver enzymes want to make compounds less toxic ... hence it tries to "detoxify" 17-aa when you take these; however, often they end up "activating" certain compounds and making them mutagenic when they initially were not. One example is benzene ... its not itself mutagenic, but when acted upon by liver enzymes, it will kick your ass.
They incubate these plates and wait to see what happens. Basically, they are waiting to see if YFC causes bacterial growth ... how does this happen you say? THE BACTERIA ARE MUTATED AND SHOULD NOT GROW!!!
If YFC with the liver extract is mutagenic ... it will cause a REVERSE mutation in the bacteria, restoring their ability to grown on MINIMAL MEDIA. The idea is translatable to people. In general, since you are healthy and have few mutations, the idea is that YFC compound tested, if it causes REVERSE mutations in bacteria, it will cause FORWARD mutations in you. And hence, it will kick YOUR ass.
However, the AMES test is old and has several inherent limitations. Here is why its NOT a good test for DNP.
a) The AMES test is only designed to Identify that a substance is a carcinogen, not establish that a compound is NOT carcinogenic. Proving a negative response is VERY difficult in science. A good analogy for this is the Roswell saying "absence of evidence is not evidence of absence." ...
b) DNP acts directly by blowing up the proton gradient established in the mitochondria. This really isnt all that important except to understand that it acts in mitochondria. however, you need to know BACTERIA DONT HAVE MITOCHRONDRIA! So how can it cause mutations in bacteria when they dont have the target of the compound?
Its well established that DNP dramatically increases the oxidative load on cells. IT is well established that oxidative stress correlates to an increased risk for carcinogenesis. I therefore conclude nothing shows DNP is safe AT ALL, and should be regarded with EXTREME CAUTION.
NFG
Something to also note is cancer is a very additive disease. THrough the course of your lifetime, you accrue many mutations in your somatic cells. Most of these will apoptose or die off. Some will not. It takes a certain "critical mass" of mutations for cells to become carcinogenic. In many cases, this is between 5-7 mutations. This is termed the "multi-hit hypothesis" and is generally accepted in scientific circles.
smokinghawk
New member
AMES should not be the sole test for DNP (and perhaps not even a test at all). But dismissing AMES does not also dismiss all the other published, peer-reviewed medical tests that find DNP to ATTACK tumors (rather than causing them), and to attack resistance bacteria, and to PROTECT cells from mutagens/mutations.
Okay, so we can dispense with AMES, but that doesn't dispense with the other medical info that says some NICE things about DNP, too.
Am I saying DNP is safe as Flintstones vitamins? Heck, no. But I'm saying that if we want honest information, we need to emphasize the "honest" as well as the "information," and HONESTLY, not all the data on DNP is bad. Some is; a lot isn't.
Okay, so we can dispense with AMES, but that doesn't dispense with the other medical info that says some NICE things about DNP, too.
Am I saying DNP is safe as Flintstones vitamins? Heck, no. But I'm saying that if we want honest information, we need to emphasize the "honest" as well as the "information," and HONESTLY, not all the data on DNP is bad. Some is; a lot isn't.
smokinghawk said:
Some of the mods are promoting dnp to be safer than ephedrine blah blah, and when asked what about free radicals??? They will say, "oh take your vitamins" ... and also never fail to bring up that dnp passed the AMES test. Then some of their parrots go on and repeat that dnp passed the ames test so it can't cause cancer.
All I want is for some people to be more curtious of other peoples' LIVES. Most of us here aren't chem majors nor are even interested in the area to study it, so this means the moderators have a good deal of responsibility ... at least the ones that claim to be a "guru" on the subject.
-sk
MrMakaveli
New member
From Andy13:
By now, every one knows that DNP acts at the powerhouse of the cell, the mitochondria. DNP causes the disipation of the proton motive force which makes ATP synthesis by oxidative phosphorilation less efficient. That means that your electron transport system of generating the proton gradient that drives the synthesis of ATP has to work a whole lot harder to make the same amount of ATP.. That's exactly why your metabolism gets boosted!
The problem here is that all the DNA in the cell is not entirely in the nucleus. Mitochondria have their own DNA as well. And mitochondrial DNP codes for some of the mitochondrial proteins that aid in metabolism and a whole host of other things.
What happens during oxidative phosphorilation (making ATP from the proton gradient) is that, in the end, molecular oxygen gets reduced to water. Sometimes, this doesn't go so well and peroxides instead of water form in the mitochondria. These are harmful free radicals that cause mutations in mitochondrial DNA. So, you say, "no problem, I'll just load up on my alpha lipoic acid and it's all good, right?'' Unfortunetly, WRONG. NO antioxidant can enter the mitochondria inner membrane. It's impermeable to everything but O2 water and CO2. And free radical formed inside the mitochondria runs wild inside changing everything from the membrane to the mitochondrial DNA.
While cancer is associated with NUCLEAR DNA mutations, parkinson's disease, general aging, alsheimer's and the things about old people that make them OLD (like reduced motor skills, hearing loss) is caused by mutations in mitochondrial DNA.
People who have a genetic predisposition to diseases like parkinson's, alzheimer's and huntington's disease tend to fuck up that reduction of molecular oxygen to water a bit more often that others. These people should re-think DNP use.
By now, every one knows that DNP acts at the powerhouse of the cell, the mitochondria. DNP causes the disipation of the proton motive force which makes ATP synthesis by oxidative phosphorilation less efficient. That means that your electron transport system of generating the proton gradient that drives the synthesis of ATP has to work a whole lot harder to make the same amount of ATP.. That's exactly why your metabolism gets boosted!
The problem here is that all the DNA in the cell is not entirely in the nucleus. Mitochondria have their own DNA as well. And mitochondrial DNP codes for some of the mitochondrial proteins that aid in metabolism and a whole host of other things.
What happens during oxidative phosphorilation (making ATP from the proton gradient) is that, in the end, molecular oxygen gets reduced to water. Sometimes, this doesn't go so well and peroxides instead of water form in the mitochondria. These are harmful free radicals that cause mutations in mitochondrial DNA. So, you say, "no problem, I'll just load up on my alpha lipoic acid and it's all good, right?'' Unfortunetly, WRONG. NO antioxidant can enter the mitochondria inner membrane. It's impermeable to everything but O2 water and CO2. And free radical formed inside the mitochondria runs wild inside changing everything from the membrane to the mitochondrial DNA.
While cancer is associated with NUCLEAR DNA mutations, parkinson's disease, general aging, alsheimer's and the things about old people that make them OLD (like reduced motor skills, hearing loss) is caused by mutations in mitochondrial DNA.
People who have a genetic predisposition to diseases like parkinson's, alzheimer's and huntington's disease tend to fuck up that reduction of molecular oxygen to water a bit more often that others. These people should re-think DNP use.
SofaGeorge
New member
Excellent post. You are a great asset to the boards.
Good points.
All other Phenols and benzene compounds have tested positive as carcinogens, but DNP stays negative....
Now after reading what you have stated, i will concede that the AMES test is not a proof, but the fact that DNP was negative to other phenols is a good thing. Michtochondrial mutation wont neccesarialy mean reproduction of a malignant cell line, the nuclear DNA hasent been mutated.
Also, like was stated, it takes around 7 mutations in a DNA strand to make cells malignant, where is there any proof if any that DNP will even cause 1 ot these mutations.
In terms of DNP being used as an anti cancer drug, i believe it was because of the body's increase in temp and the tendancy of malignant tumors to be more temperature sensitive than other body tissues.
NFG, could i email you about this type of thing, im trying to decide where to tak emy education and this is the type of thing im interested. Ill start with a mico or molecular bio first though....
I also want to know something else.....
The body destroys mutated cells with the immune system.
why does a mutated cell last long enough to become malignant and then why is it not killed by the immune system?
Cancer is a VERY interesting topic for me, its killed very important people to me, so any knowledge on it is appreciated...
All other Phenols and benzene compounds have tested positive as carcinogens, but DNP stays negative....
Now after reading what you have stated, i will concede that the AMES test is not a proof, but the fact that DNP was negative to other phenols is a good thing. Michtochondrial mutation wont neccesarialy mean reproduction of a malignant cell line, the nuclear DNA hasent been mutated.
Also, like was stated, it takes around 7 mutations in a DNA strand to make cells malignant, where is there any proof if any that DNP will even cause 1 ot these mutations.
In terms of DNP being used as an anti cancer drug, i believe it was because of the body's increase in temp and the tendancy of malignant tumors to be more temperature sensitive than other body tissues.
NFG, could i email you about this type of thing, im trying to decide where to tak emy education and this is the type of thing im interested. Ill start with a mico or molecular bio first though....
I also want to know something else.....
The body destroys mutated cells with the immune system.
why does a mutated cell last long enough to become malignant and then why is it not killed by the immune system?
Cancer is a VERY interesting topic for me, its killed very important people to me, so any knowledge on it is appreciated...
Now we shouldnt go around yelling "DNP can cause cancer" and shit....
The truth is, the AMES test is/was vastly used to detect carcinogens and DNP passed the test.
Instead of stating reasons as to why DNP isnt a good candidate for the AMES test, how about showing us proof that DNP IS carcinogenic.
Are you ready to base your opinions off of one persons belief on how the AMES test is inadiquate?
The truth is, the AMES test is/was vastly used to detect carcinogens and DNP passed the test.
Instead of stating reasons as to why DNP isnt a good candidate for the AMES test, how about showing us proof that DNP IS carcinogenic.
Are you ready to base your opinions off of one persons belief on how the AMES test is inadiquate?
Another thing, just becase somthing can act as an antineoplastic agent, doesnt mean its incapable of geing mutanagenic.
Take for example the Cis isomer of Pt(Cl)2(NH3)2, otherwise known as Cis-Platin. This is a widely used chemotherapy drug effective against all kinds of cancers. It targets fast proliferating cells such as cancer cells (and bone marrow, hair ect). It is a square planar molecule that is an intercalating agent meaning it can slide itself into a DNA strand dissrupting it, damaging, mutating it, and killing the cell, or stoping its reproduction as was seen in Cis-platins earlier days (hopefully, mostly cancer cells). Bad thing is, it can mutate non cancerous cells.
Just becasue DNP acts agains cancer cells (through a specific pathway) doesnt mean that it can be carcinogenic (through another pathway).
But, the AMES test is what we have to go on at this point.
Take for example the Cis isomer of Pt(Cl)2(NH3)2, otherwise known as Cis-Platin. This is a widely used chemotherapy drug effective against all kinds of cancers. It targets fast proliferating cells such as cancer cells (and bone marrow, hair ect). It is a square planar molecule that is an intercalating agent meaning it can slide itself into a DNA strand dissrupting it, damaging, mutating it, and killing the cell, or stoping its reproduction as was seen in Cis-platins earlier days (hopefully, mostly cancer cells). Bad thing is, it can mutate non cancerous cells.
Just becasue DNP acts agains cancer cells (through a specific pathway) doesnt mean that it can be carcinogenic (through another pathway).
But, the AMES test is what we have to go on at this point.
bigrand said:
Wow... Now this is a guy who has done some reading!
Just a few things to add...
There is a difference between a "mutagen" and a "carcinogen." A "mutagen" is generally thought to pocess intrinsic DNAmutating abillity-- these are detected by the Ames test. On the other hand, a compound can result in cancer but cause no direct or intrinsic mutations in DNA. A good example of this is an analog of diaclylglycerol (I forget the name). It is not readily degraded, at least nearly as fast as DAG, and results in unregulated growth.. Let us not forget that a cell that has lost the ability to control it's growth is the stuff that tumors are made of. In the case of the DAG analog, no DNA mutagenesis occurs, yet the cell becomes cancerous.
Now, cis-platinum, on the other hand, causes cell death but in a different mechanism than pure DNA mutation. This cell death is acutally systematic cell suicide (apoptosis). Cis-platinum induces tumor supressor protein p53, which is the biological kommisar. P53 induction is well characterized in the face of DNA damage caused by uv radiation or chemical agents such as etoposide and cis-platinum. Acutally though, p53 is sometimes induced in the absence of DNA damage, but that is going beyond the scope. The point is: an increase in p53 causes an up-reguation of machinery required for DNA repair, cell cycle arrest, or programed cell death. Does DNP increase p53 levels?
Does DNP cause an increase in reactive oxygen species derived from aerobic metabolism? I used to think so... But now I'm not so sure. An increase in membrane potential or electrochemical gradient in the mito caused inhibition of one of the carriers (cyanide) results in a blockade of electron carrying intermediates. When the half life of one of these intermediates (ubquinone) is increased, it can result in deviant reductions of O2 to superoxide radical--- this fucks shit up.. not just in the mito, but also in the cell (I was wrong before when I said that superoxides formed in the mito stay there).
Now, the interesting thing, and something I carelessly over-looked before is the case during REDUCED membrane potential... This is the scinario DNP causes... A reduced membrane potential may actually result in a reduction in reactive oxygen species.. In vitro? Perhaps. In vivo? Who knows.. I think it's doubtful that a measurable reduction could occur.. But I don't know. If you like, I encorage you to search medline for this...
Bottom line:
Passing the Ames test does not mean a compound cannot cause cancer.... Cadmium is a great example of an agent that has little to no mutagenic power... yet is a carcinogen.
Also- Take your anti-oxidants! NAC has been shown to protect DNA from damage caused by cigarette smoke. Will ALA work in this respect as well? Probably.
Andy
bigrand said:
Andy has obviously done graduate work. Im sure he holds a PhD. Otherwise, Im impressed as shit. p53 isnt a cytochrome. And p53 is mutated in a number of cancers period since is a tumor suppressor, loss of a tumor suppressor promotes cancer growth in most cases. Also, Andy, there are many characterized non p53 mediated paths to apoptosis. Rb is a good example. Also, p21 which is normally thought to act in a p53 pathway has been shown to have apoptotic effects independent of p53. Great discussion on mutagen vs carcinogen. Well put. Another example would be anything that constitutively actives the MapK family or Ras ... doesnt need to cause a mutation but can be growth promoting, destroy a cell cycle checkpoint, increase cellular invasion and adhesion (differential regulation of integrins) ... there are a number of factors. Point is: DNP isnt safe for a number of reasons, if you want to talk about hyperpyrexia, everyone will agree ... cancer ... maybe there is some dispute ... however, whatever your goal is in weight loss, there are safer methods to achieve it than by going down the DNP pathway...gotta love those ICE ENEMAS!
I just wish i knew where to look myself to try to figure this shit out myself. My bad on the cytochrome thing, i havent talked about p53 or Ras-Onc or any of that shit in years (i didnt really know much about it anyway, except that there was an overexpression in pancreatic cancer cells). Junior college isnt teaching me too much about this shit, its up to you bros to fill me in!!!!
I understand DNP can be very dangerous, im just scared shitless of cancer for obvious reasons. I know oncologists cant help me if i get it anyway, so i definetly dont want to get it from DNP.
From what i was gathering, there is no real evidence DNP can cause cancer.
BTW....i thought the main reason of cisplatin's ability to kill cancer cells is its ability to bind into the helix and make bonds that dont redially dissacociate(intercalating agent), making adducts and killing the cell (inhibition of DNA synthesis)? And a reason for cisplatin (and carboplatin) resistance is the ability of the cancer cells to repair the adduct........damnit i dont know, ill have to go check.
Anyway, let me know how wrong i am NFG and Andy, im trying though!!!!
I understand DNP can be very dangerous, im just scared shitless of cancer for obvious reasons. I know oncologists cant help me if i get it anyway, so i definetly dont want to get it from DNP.
From what i was gathering, there is no real evidence DNP can cause cancer.
BTW....i thought the main reason of cisplatin's ability to kill cancer cells is its ability to bind into the helix and make bonds that dont redially dissacociate(intercalating agent), making adducts and killing the cell (inhibition of DNA synthesis)? And a reason for cisplatin (and carboplatin) resistance is the ability of the cancer cells to repair the adduct........damnit i dont know, ill have to go check.
Anyway, let me know how wrong i am NFG and Andy, im trying though!!!!
Last edited:
NFG123 said:
Exactly.. p53 is non-functional in 50% of tumor cells! This alone illustrates it's importance.
I agree that there are p53 independent apoptotic pathways, but I never knew p21, classically induced by p53, and generally considered "anti-apoptotic" (by causing an arrest in growth) was one.
Aside, I think Lithium may be a focus for future thereputic intervention--- very interesting stuff. Li+ inhibits glycogen synthase kinase-3 (GSK-3). GSK-3, as of late, has been viewed as "pro-apoptotic" and is a player in the wnt signalling pathway.. Li+ has been shown to protect neuro cells from apoptosis in the face of glutamate and other neuro toxic agents by blocking GSK-3. In addition, over-expression of GSK-3 leads to an increased release of cytochrome c into the cytosol--- prime apoptotic behaviour here.
I look for Li+ to take on a larger pharmaceutical role in the future-- possibly as Alzsheimer's and Parkinson's disease therapies and/or part of cancer therapy.
NFG- you obviously know your stuff.. What is your background?
Andy
I guess ill finish out this current DNP cycle and then stick to thermorexin, there are way too many questions about DNP (looking through medline, i found hundreds of abstracts on DNP and its action on tumor cell, some seemed good, while others seemed bad, just too much shit for me to understand, so ill stick with the simpiler stuff).
MrMakaveli
New member
This def belonges in Best of Elite
MrMakaveli
New member
sk* said:
Noooo, not everyone can access that forum and the great responces won't keep coming ... not to mention the great information will be lost to most.
-sk
I met after its dead and buried...although you have a very good point
bigrand said:
A simple in vitro expt could be done.. I think I could have such data gathered, but it would COST time.. ANd I'm not positive the demand is high enough...
A general tissue culture viability expt along with p53 Western would get us started... A Western will tell us if p53 is up-regulated or not. An increase in this protein is usually a good indicator of bad things occuring in the cell. Such things that would warrant DNA repair, apoptosis machinery.
If this data becomes interesting, co-treatment with anti-oxidants and/or other drugs may provide more feedback.
Like I said, I would be willing to see it done.. And it would not be any real expense to an appropriately equipped lab.. But time is money.
Andy
Last edited:
Andy,
Would a change in p53 be the only other indicator of a cell line possibly becoming malignant? Im assuming that there are no other mutations caused by DNP, so it would have to be a change to a tumor suppressor gene...or some other important gene?
PS.... wouldnt that gene need to be downregulated or turned off if it is a tumor supressor gene?
All the abstracts i have been reading have been DNPs effects in more of a broad sense, such as its effects on various intra and extra cellular reactions, not on the DNA level, so i agree, this test of yours would be quite informative.
Would a change in p53 be the only other indicator of a cell line possibly becoming malignant? Im assuming that there are no other mutations caused by DNP, so it would have to be a change to a tumor suppressor gene...or some other important gene?
PS.... wouldnt that gene need to be downregulated or turned off if it is a tumor supressor gene?
All the abstracts i have been reading have been DNPs effects in more of a broad sense, such as its effects on various intra and extra cellular reactions, not on the DNA level, so i agree, this test of yours would be quite informative.
Last edited:
Ceebs
New member
Andy13 said:
Chalk another line on the high demand tally from me. This information would be invaluable to anyone who's ever used DNP, or thought about it. Even if I didn't have a personal reason for wanting to know, I'd still think it's interesting from a purely scientific point of view.
bigrand said:
It often takes time (days, months, years?) of exposure to some carcinogen before it acutally causes malignant growth.. A Western blot for p53 is a quick and very good way to take a snapshot of the cell and get an idea of what's going on. p53 is responsible for causing DNA-repair enzymes to be up-regulated, it also induces proteins needed for cycle arrest and apoptosis.. P53 is truely the biological police detective. Just like a bunch of cop cars showing up in your neighborhood is usually a good indicator that something is not quite right, an increase in p53 from the low-low levels normally seen in a cell is likewise a signal that the cell is under some sort of genomic threat, uv light, carcinogens, etc. Actually, DNA strand breaks themselves are known to induce p53. Detection of this 'first response' against cell damage by measuring p53 induction is used quite often in oncology.
Andy
So, this gene, if overactive, is a signal that there is some sort of potential damage to the DNA? This test will tell us that DNP is/isnt causing some sort of genomic stress, correct?
Damn, i thought we would have to find WHERE the damage took place and if it was a missense, nonsense, frameshift mutation, whatever.....This is the OVERALL indicator of genomic damage, i guess specifics arent neccesary, only when determining how to treat malignant tissue..?
Damn, i thought we would have to find WHERE the damage took place and if it was a missense, nonsense, frameshift mutation, whatever.....This is the OVERALL indicator of genomic damage, i guess specifics arent neccesary, only when determining how to treat malignant tissue..?
bigrand said:
There's a chance that DNP could induce p53 while no genomic damage is taking place, likewise, there is also a chance that DNP could be a major threat to the cell while p53 is NOT induced.. But these possibilities are rather small. Induction of p53 classically occurs when the cell is under attack. Without this gene, DNA repair is compromised with a reduced ability to arrest growth and/or commence cell suicide (since p53 plays well-known roles in these processes).
Curious, if p53 is active it can repair DNA if damaged and "induce apoptosis", correct?
Why when in malignant cell line with overexpressed p53, there is no apoptosis? Is it because the p53 gene is mutated to where there is no apoptosis, but the genen is still active in DNA repair?
Thinkin about this one for a few days ive been....
Why when in malignant cell line with overexpressed p53, there is no apoptosis? Is it because the p53 gene is mutated to where there is no apoptosis, but the genen is still active in DNA repair?
Thinkin about this one for a few days ive been....
bigrand said:
It could be the case that one of the downstream mediators of apoptosis is non-functional.. Also, I'm sure there are a host of cellular triggers that influence p53's decision to induce apoptosis, or cell cycle arrest. Additionally, post-transcriptional regulation of p53 is very important, and helps the protein to become active and also regulates it's half life..
Andy
bigrand said:
You know, I cannot say for sure... Safe for BBers to self administer? No way.. Safe for people to use under the care of a physician? I still don't think we can be absolutely sure..
Everybody and his brother and sister have used DNP while managing to keep themselves out of an emergency room or funeral home. But it's those exceptions that raise all kinds of question marks.. Are the less-lucky one's representative of a % of the population that are extremely sensitive to the drug or are they (Darwinistic style) victems of their own stupidity? We will never know with out (much) more credible research.
Andy
Lumberg, how do you figure?
All im saying is even though the AMES test might not be a good test to determine whether DNP is a carcinogen, there is no known evidence that proves DNP IS carcinogenic.
I understand that just because DNP passed the test, in this case, doesnt prove that its not carcinogenic, but that doesnt mean that it IS.
So, now we are at a point of unknown, but judging by the history of use in medicine in two cases ive read (one old and one more modern), people shouldnt fear for their lives after using DNP.
"Why the AMES test does not say DNP is safe"..........where is it said that it ISNT safe?
All im saying is even though the AMES test might not be a good test to determine whether DNP is a carcinogen, there is no known evidence that proves DNP IS carcinogenic.
I understand that just because DNP passed the test, in this case, doesnt prove that its not carcinogenic, but that doesnt mean that it IS.
So, now we are at a point of unknown, but judging by the history of use in medicine in two cases ive read (one old and one more modern), people shouldnt fear for their lives after using DNP.
"Why the AMES test does not say DNP is safe"..........where is it said that it ISNT safe?
Yeaup, sounds good Andy. In this case, the AMES test doesnt tell us shit about DNP. It doesnt prove it isnt a carcinogen, but there is nothing else proving it is.
"All drugs that fail the Ames test are carcinogens but not all carcinogens fail the Ames test."
I just didnt want people to start believing the last part. "oh no, DNP IS one of those carcinogens that passed"
Nobody said it IS a carcinogen........
Well, as of now, im going just for my BS in Microbiology or Molecular biology (will decide in a few months). Then, either medschool, or graduate nursing program (have all the pre-recs done to go into the program, and it pays good as hell while im still involved with medicine).
It will stay medicine, but im not POSITIVE as to where in medicine because everyday, i learn something new i want to persue (like the info in this thread).
"All drugs that fail the Ames test are carcinogens but not all carcinogens fail the Ames test."
I just didnt want people to start believing the last part. "oh no, DNP IS one of those carcinogens that passed"
Nobody said it IS a carcinogen........
Well, as of now, im going just for my BS in Microbiology or Molecular biology (will decide in a few months). Then, either medschool, or graduate nursing program (have all the pre-recs done to go into the program, and it pays good as hell while im still involved with medicine).
It will stay medicine, but im not POSITIVE as to where in medicine because everyday, i learn something new i want to persue (like the info in this thread).
Last edited:
I wish i could say for certian how safe DNP is, but the fact is there hasnt been enough research (at least with regards to carcinogenity, according to what was stated about the AMES test) to say for sure. Im going with what is documented, both medically and through the underground. I say its still safe to use if you know what you are doing and you do it in short cycles.
Maybe oneday, I will be in a position to find out for sure with a future education and the right equipment, that is unless someone beats me to it....
Maybe oneday, I will be in a position to find out for sure with a future education and the right equipment, that is unless someone beats me to it....
bigrand said:
It could so easily be done... And the materials required are cheap for the well-equiped lab..
The problem is: I don't believe it would be publishable material.. unless it was incorporated into a larger manuscript. But who knows...
It's asking a lot of someone to take the time to run these assays for nothing. Of course, it is VERY interesting and worthy for us.. and may even stem an idea for a publishable paper... but it may be hard to convince someone of this.
Andy
Well, with DNPs history as a prescribed fat burner, it might not be so far fetched. There is already a good amount of info on it, i mean, its carcinogenity has never really been questioned when it was used before until now and it seems to respect the bodys organs like the liver and kidneys and such. There is currently research with human uncoupling protiens anyway, DNP could be a model for that???
Why has the carcinigenity issue never come up before? Why has it not been discussed until now on this board? That seems to be the real question mark with regards to DNP therapy...
Why has the carcinigenity issue never come up before? Why has it not been discussed until now on this board? That seems to be the real question mark with regards to DNP therapy...
MrMakaveli said:
Mitochondrial protection:
5g ALCar + 600mg R-ALA + 100mg Co-Q10 + 3g Vit.C + 800IU Vit. E.
That protects your mitochondria from oxidative damage.
If you want, you can substitute Co-Q10 for idebenone(More potent synthetic form) 45-60mg.
Oh and btw, R-ALA recycles both Vit. C and Vit. E and is itself both fat and water soluble(A phospholipid).
Fonz
So basically what I gather from that is AMES is not the correct test to guage accurately if DNP has the ability to cause cancer. Great read and interesting in that biochemistry has so many correlational components that we might never truly find a link from DNP to cancer.
DIV
DIV
GoldenDelicious
New member
i dont know where i was reading it but DNP use does indeed cause a rise in p53 expression, which as andy said earlier on, warrants further investigation
at the end of the day it is interesting to take a look at the lifespans of the men who were exposed to the stuff back in WW2...again i dont know where i was reading it but there was not a significant deviation in their overall life span, which i believe was actually in the 60+ year range
furthermore, in the work done by...bloody hell that american guy who put together most of the DNP information back in the 30s.....aaargh it was him and another guy....anyway i did not see any indication of any increased incidence of anything except cataract formation in women. the carcinogenicity of phenols would have been well known even then, and i would assume taht a man of his calibre would have examined the issue. although assumptions arent the greatest things to make in the realm of medical science. someone with a working subscription to medline, download som articles for me
personally the issues for me regarding DNP is the structural and chemical similarity to known carcinogens - namely the other phenols - and also the p53 induction. apart from that, i think that DNP has earned a very sinister name because 1) it works, and works very very well, and as i have seen professionally, the better something works, the "stronger" people think it is, and therefore, the more dangerous, and 2) it has been associated with numerous deaths in the past, DESPITE the fact that the mechanism by which death was caused (overheating, dehydration, hypoglycaemia, coma and organ collapse) is independent of the cancer issue that we are talking about in the here and now
at the end of the day, many, many people used DNP in the past, with few ill effects that were discernible in and post analysis of the study group - although importantly, i have not seen the study protocols used by that american researcher
something else to consider is that there are many other electron uncouplers used commonly throughout the world - the illicit party drugs MDMA (ecstasy) and also, PMA (which is another drug made by a lot of bozos thinking that they have actually made MDMA, when reallym they screwed it all up and made the wrong thing) and really, we are talking about some serious long term, fairly high dosing- i personally know people who do it every single weekend, and sometimes during the week - and i travel in fairly tame circles, so im sure lots of other people use these drugs even more heavily. anyway the issue of plain old electron uncoupling and resultant oxidative stress etc is quite a common phenomenon, and i havnt heard anything too overt in terms of malignancy...and believe me, if it was an issue, the various lobby groups would be screaming blue murder about it. i just dont see it as being as significant as DNPs structural similarity to other phenols, is all.
anyway. interesting thread. cutting edge has a few of these, that got quite interesting
cheers
at the end of the day it is interesting to take a look at the lifespans of the men who were exposed to the stuff back in WW2...again i dont know where i was reading it but there was not a significant deviation in their overall life span, which i believe was actually in the 60+ year range
furthermore, in the work done by...bloody hell that american guy who put together most of the DNP information back in the 30s.....aaargh it was him and another guy....anyway i did not see any indication of any increased incidence of anything except cataract formation in women. the carcinogenicity of phenols would have been well known even then, and i would assume taht a man of his calibre would have examined the issue. although assumptions arent the greatest things to make in the realm of medical science. someone with a working subscription to medline, download som articles for me
personally the issues for me regarding DNP is the structural and chemical similarity to known carcinogens - namely the other phenols - and also the p53 induction. apart from that, i think that DNP has earned a very sinister name because 1) it works, and works very very well, and as i have seen professionally, the better something works, the "stronger" people think it is, and therefore, the more dangerous, and 2) it has been associated with numerous deaths in the past, DESPITE the fact that the mechanism by which death was caused (overheating, dehydration, hypoglycaemia, coma and organ collapse) is independent of the cancer issue that we are talking about in the here and now
at the end of the day, many, many people used DNP in the past, with few ill effects that were discernible in and post analysis of the study group - although importantly, i have not seen the study protocols used by that american researcher
something else to consider is that there are many other electron uncouplers used commonly throughout the world - the illicit party drugs MDMA (ecstasy) and also, PMA (which is another drug made by a lot of bozos thinking that they have actually made MDMA, when reallym they screwed it all up and made the wrong thing) and really, we are talking about some serious long term, fairly high dosing- i personally know people who do it every single weekend, and sometimes during the week - and i travel in fairly tame circles, so im sure lots of other people use these drugs even more heavily. anyway the issue of plain old electron uncoupling and resultant oxidative stress etc is quite a common phenomenon, and i havnt heard anything too overt in terms of malignancy...and believe me, if it was an issue, the various lobby groups would be screaming blue murder about it. i just dont see it as being as significant as DNPs structural similarity to other phenols, is all.
anyway. interesting thread. cutting edge has a few of these, that got quite interesting
cheers
Last edited:
Underexpression of p53 (or a null expression) is what we dont want since active p53 regulates apoptosis. A nonfucntional p53 is seen in about half of all cancers. It can be somewhat reactivated using a retro-inverso copy of wildtype p53 attatched to TAT (surface protein from HIV virus) to shuttle it into the cell.
The functional groups attatched to benzene rings and phenol can alter the compound to make it less reactive with DNA and less carcinogenic, that seems to be the case with 2,4
The functional groups attatched to benzene rings and phenol can alter the compound to make it less reactive with DNA and less carcinogenic, that seems to be the case with 2,4
DNP is a non-coupler.
When you burn calories, energy is trapped in the body in the form of highenergy phosphate bonds (ATP). When energy is used, these high energy phosphate bonds are used up to create AMP or ADP.
When you use DNP, ATP is not created, and energy is lost as heat.
DNP kills by cause high fever.
There had been several deaths, mostly with high fever, with DNP before it was pulled from the market.
When you burn calories, energy is trapped in the body in the form of highenergy phosphate bonds (ATP). When energy is used, these high energy phosphate bonds are used up to create AMP or ADP.
When you use DNP, ATP is not created, and energy is lost as heat.
DNP kills by cause high fever.
There had been several deaths, mostly with high fever, with DNP before it was pulled from the market.
Yep, specifically in the ETC, the H+ gradient is dissrupted and the H+ are released from the membrane=entropy.
Yeah, i was looking through my old posts and saw this one. With all the posts on DNP and the lack of knowledge of people using it latley, i figured id bump it up for a read.
I too look for the meaning of life, and my BS.
Yeah, i was looking through my old posts and saw this one. With all the posts on DNP and the lack of knowledge of people using it latley, i figured id bump it up for a read.
I too look for the meaning of life, and my BS.
DNP or any oxidative uncopuler destroys the membrane - or at very small concentrations destoyed - the proton gradient change I in the inner part of mitochondrial membrane. Cells continue to oxidize food molecules to feed electrons into the electron-transport chin, but H+ ions pumped across the membrane flow back into the mitochondria in futile cycle. Their energy cannot be tapped to drive ATV synthesis, and hence is released as heat. Patients who have been given small doses of DNP lose weight because their fat reserves are used more rapidly to feed the electron-transport chain, and the whole process simply “wastes” energy.
A similar mechanism of heat production I used by specialized tissue composed of brown fat cells, which is abundant in newborn humans and in hibernating animals. These cells are packed with mitochondria that leak part of their H+ gradient futilely back across the membrane for the sole purpose of warming up the organism. These cells are brown because they are packed with mitochondria, which contain high concentrations of pigmented proteins, such as cytochromes.
The DNP collapses the electrochemical proton gradient completely. H+ ions that are pumped to one side of the membrane flow back freely, and therefore no energy can be stored across the membrane.
An electrochemical gradient is made up of two components: a concentration gradient and an electrical potential. If the membrane is made permeable to K+ with migraine, K+ will be driven into the matrix by the electrical potential of the inner membrane ( negative inside, positive outside). The influx of positively charged K+ will abolish the membrane’s electrical potential . In contrast, the concentration component of the H+ gradient ( the PH difference ) is unaffected by ingrain. Therefore, only part of the driving force that makes it energetically favorable for H+ ions to flow back into the matrix is lost.
DNP can change protein expression if it caused any frameshifit/deletion/ insertion mutation. a frameshift mutation (also called a frameshift or a framing error) is a mutation that inserts or deletes a single nucleotide from a DNA sequence. Due to the triplet nature of gene expression, the insertion/deletion can disrupt the grouping of the codons, resulting in a completely different translation (Translation_(genetics)) from the original.
A similar mechanism of heat production I used by specialized tissue composed of brown fat cells, which is abundant in newborn humans and in hibernating animals. These cells are packed with mitochondria that leak part of their H+ gradient futilely back across the membrane for the sole purpose of warming up the organism. These cells are brown because they are packed with mitochondria, which contain high concentrations of pigmented proteins, such as cytochromes.
The DNP collapses the electrochemical proton gradient completely. H+ ions that are pumped to one side of the membrane flow back freely, and therefore no energy can be stored across the membrane.
An electrochemical gradient is made up of two components: a concentration gradient and an electrical potential. If the membrane is made permeable to K+ with migraine, K+ will be driven into the matrix by the electrical potential of the inner membrane ( negative inside, positive outside). The influx of positively charged K+ will abolish the membrane’s electrical potential . In contrast, the concentration component of the H+ gradient ( the PH difference ) is unaffected by ingrain. Therefore, only part of the driving force that makes it energetically favorable for H+ ions to flow back into the matrix is lost.
DNP can change protein expression if it caused any frameshifit/deletion/ insertion mutation. a frameshift mutation (also called a frameshift or a framing error) is a mutation that inserts or deletes a single nucleotide from a DNA sequence. Due to the triplet nature of gene expression, the insertion/deletion can disrupt the grouping of the codons, resulting in a completely different translation (Translation_(genetics)) from the original.
what scare more more than cancer is that DNP can raise body tempreture. enzymes are turned off and on at certain body tempretures , if change of in tempreture trigered some not common inactive enzymes then it can cause a real problem.
also big increase in body temp can cause tissue damage of certain organs that are heat sensitive like heart, liver, kidneys, and most impartant the brain.
also big increase in body temp can cause tissue damage of certain organs that are heat sensitive like heart, liver, kidneys, and most impartant the brain.
Maetenloch
New member
x_muscle said:
With normal use DNP the core body temperature doesn't go up - the body is able to compensate by (excessive) sweating. So enzyme activation or tissue damage would only be an issue during an overdose of DNP.
a-bomb5083
New member
*hand not raised*
DNP does raise body temp. The entropy created by H+ release (remember, this is happening constantly) increases core temp and temp of surroundings because of heat emmission.
Taken in a moderate dose, the temp increase is similar to having a slight fever, it shouldnt go up too high.
So far, all evidence points to DNP not causing mutations.
Maybe it does mutate but there is a spontaneous back mutation which corrects the codon.............but not likley, actually id say no way.
Taken in a moderate dose, the temp increase is similar to having a slight fever, it shouldnt go up too high.
So far, all evidence points to DNP not causing mutations.
Maybe it does mutate but there is a spontaneous back mutation which corrects the codon.............but not likley, actually id say no way.
P
PolfaJelfa
Guest
I dont need any studies. Anyone who thinks DNP is safe, is kiding only themselves!
Nobody said its safe, but its effective and somewhat safe if taken properly. AAS arent safe, anyone who says that is kidding themselves. EVERY pharmaceutical and chemical has its plusses and minuses, DNP moreso than others, but all can be harmfull. Ive done several DNP cycles with no problems, and ive done them with problems. Point is, it CAN be done relativly safely.
If people looked it up on medline, DNP is a fascinating compound with many effects, possitive and some negative.
If people looked it up on medline, DNP is a fascinating compound with many effects, possitive and some negative.
krishna
New member
bigrand said:
Comparing AAS to DNP as far as being safe is completely ludicrous! People die from direct effects of DNP use. It is an industrial chemical used in pesticides and toxic water treatment. It was not designed to be used in the body. The reason you lose weight on it is because it's killing you. It adversely affects every organ in your body. AAS if used properly are indeed safe and can even provide health BENEFITS! The FDA won't even approve DNP to be a prescription. Please tell me you're not stupid enough to say DNP is as safe as AAS. The amount it takes for DNP to be effective is very close to the amount it takes to KILL YOU! In no situation whatsoever can that ever be safe!
Dude, i said DNP is dangerous MORESO than others like AAS.
My point is that DNP HAS and WILL continue to be used without major consequence. ANd no, it isnt killing you, its compromising the way you make energy, TEMPORARALY.
200-400mg wont kill you. Read up on how it works and its metabolism and disposal in the body and you will see its not KILLING you. youd be suprised what a lot of pharmeceuticals do to you, you would consider it "killing" you.
Re read my post, its not as boneheaded as you think. Key words, somewhat, relativly, CAN, HAS, moreso.......
My point is that DNP HAS and WILL continue to be used without major consequence. ANd no, it isnt killing you, its compromising the way you make energy, TEMPORARALY.
200-400mg wont kill you. Read up on how it works and its metabolism and disposal in the body and you will see its not KILLING you. youd be suprised what a lot of pharmeceuticals do to you, you would consider it "killing" you.
Re read my post, its not as boneheaded as you think. Key words, somewhat, relativly, CAN, HAS, moreso.......
I like this bigrand character. I have posted a couple threads from class about DNP.
Krishna, in reply to your post on another thread........
I take DNP becasue i understand it, know how to use it in a dose and manner thats effective for fat loss (about a lb a day). I have had negative sides, but i have learned the ins and outs to where i dont get the bad sides anymore, just the fat loss.
It isnt safe, but it doesnt have to be deadly. Happy medium, calculated risk if you may.
I take DNP becasue i understand it, know how to use it in a dose and manner thats effective for fat loss (about a lb a day). I have had negative sides, but i have learned the ins and outs to where i dont get the bad sides anymore, just the fat loss.
It isnt safe, but it doesnt have to be deadly. Happy medium, calculated risk if you may.
ive done it 5 times, weight stays of, about 7 lbs in 10 days.
I was a really fat ass after highschool with a lot to loose, so ive run it when ive gotten to points where fat loss was becoming stagnant.
ive done long 200mg and short 400mg cycles and a 600mg cycle (with allergic reaction that ive been ready for ever since).
Im at a point where ive got a good cardio regemin and not nearly the amount of fat to loose, so im staying away for now, unless i want get stagnant. Remember, the fatter, the higher set the bodys equilibrium for fat storage....harder to control weight.
I have done years of research on this (mostly through biochem classes and med shit) and i now just try to teach what ive personally learned. It works and can be relativly safe, but do your homework first, its serious shit.
I was a really fat ass after highschool with a lot to loose, so ive run it when ive gotten to points where fat loss was becoming stagnant.
ive done long 200mg and short 400mg cycles and a 600mg cycle (with allergic reaction that ive been ready for ever since).
Im at a point where ive got a good cardio regemin and not nearly the amount of fat to loose, so im staying away for now, unless i want get stagnant. Remember, the fatter, the higher set the bodys equilibrium for fat storage....harder to control weight.
I have done years of research on this (mostly through biochem classes and med shit) and i now just try to teach what ive personally learned. It works and can be relativly safe, but do your homework first, its serious shit.
hawaii50
New member
These are all good points. But have you ever heard about your bodies natural PH level determining whether you will ever get cancer or not? There was a HUGE study about it a few years back... it read something like: If your body is naturally alkaline or acidic, you'll never get cancer.. but if you're natural ph level is base.. you can get it.
I personally believe that the FDA and other groups have covered that info up. I think in the same article it mentions that it is possible to alter your Ph level naturally.. without taking those nasty cancer drugs
has anyone else heard of this? I'll try to find that article... jeez where did i put that?
I personally believe that the FDA and other groups have covered that info up. I think in the same article it mentions that it is possible to alter your Ph level naturally.. without taking those nasty cancer drugs
has anyone else heard of this? I'll try to find that article... jeez where did i put that?
krishna
New member
hawaii50 said:These are all good points. But have you ever heard about your bodies natural PH level determining whether you will ever get cancer or not? There was a HUGE study about it a few years back... it read something like: If your body is naturally alkaline or acidic, you'll never get cancer.. but if you're natural ph level is base.. you can get it.
I personally believe that the FDA and other groups have covered that info up. I think in the same article it mentions that it is possible to alter your Ph level naturally.. without taking those nasty cancer drugs
has anyone else heard of this? I'll try to find that article... jeez where did i put that?
Cancer has to do with genes that regulate cell division. Mutations in certain genes affect the division process as it is not regulated properly.
alkaline is the same as basic.
%50 of cancers have a mutated p53 gene responsible for apoptosis. Mutations to this gene rendering it null and unexpressed lead to unregulated cell growth and loss of contact inhibition. There are other genes responsible for controling apoptosis (cant remember off the top of my head), but there are other mutations involved. Changes in pH do have an effect, ie with acid reflux inducing esophageal cancer. Highly acidid environments can lead to increased incidence of cancer.
Cancer drugs arent meant to alter pH. Most anti-neoplastic agents are meant to break DNA strands and kill malignant cells, IE Cisplatin (PtCl2(NH4)2) is an intercalating agent which slides inbetween DNA and breaks it......that shit sucks, id rather go with gene reactivation if applicable.
%50 of cancers have a mutated p53 gene responsible for apoptosis. Mutations to this gene rendering it null and unexpressed lead to unregulated cell growth and loss of contact inhibition. There are other genes responsible for controling apoptosis (cant remember off the top of my head), but there are other mutations involved. Changes in pH do have an effect, ie with acid reflux inducing esophageal cancer. Highly acidid environments can lead to increased incidence of cancer.
Cancer drugs arent meant to alter pH. Most anti-neoplastic agents are meant to break DNA strands and kill malignant cells, IE Cisplatin (PtCl2(NH4)2) is an intercalating agent which slides inbetween DNA and breaks it......that shit sucks, id rather go with gene reactivation if applicable.
bigrand said:
do you know anything about the kip and cif (I think it's cif) regions of the p53 gene which are responsible for I believe sequentially phosphorylating and turning on the active region of the protein?
wow, that was a clusterfuck of a sentence.
NFG123 said:
Great post! I work in a cancer lab and have found many of these hypotheses to be true. However, though mutant cells tend to go through apoptosis until a healthy mass starts, we must not assume that it takes a long time for cancer to form. Cancer has and will develop quickly in some cases. So extreme caution should be taken when administering DNP. As it was mentioned earlier, DNP changes the proton gradient in mitochondria dramatically causing many changes in the cell biochemically and physiologically. Anyway, just my 2 cents. Good Post Though!!!
Those regions you speak of i believe are in the promotor region, responsible for begining translation of the gene, mutations in this area will change the AA sequence and the promotor will loose function=no active gene function.
Ill check, i havent gone into specific sections of the gene, only AAs around the C terminus to make a primer used turn on unactive mutant p53 (did some reading on the subject).
With DNP, the actuall result of DNP by itself is the change in permiability of the mito membrane, no electrical gradiant can be established because H+ leaks out. The problem DNP causes is secondary, free radical release from WAT, this is what could lead to a mutation, not DNP itself.
Yep, the theory is about 7 mutations to become malignant.
Some cases only require a few mutations if they are in the right places (ie a null mutation in p53 stops apoptosis).
Ill check, i havent gone into specific sections of the gene, only AAs around the C terminus to make a primer used turn on unactive mutant p53 (did some reading on the subject).
With DNP, the actuall result of DNP by itself is the change in permiability of the mito membrane, no electrical gradiant can be established because H+ leaks out. The problem DNP causes is secondary, free radical release from WAT, this is what could lead to a mutation, not DNP itself.
Yep, the theory is about 7 mutations to become malignant.
Some cases only require a few mutations if they are in the right places (ie a null mutation in p53 stops apoptosis).
