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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.
