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Not all carcinogens are mutagens. Alcohol and estrogen, for example, does not damage DNA.

It's one of the assumptions of the Ames test that mutagenicity implies carcinogenicity, but is this always the case? I assumed that it was, but then I saw one of the comments here. I did some more research but the internet seems to be reluctant to be definitive on the subject. This guy claims 'no', but I'd prefer sources or at least a response that handles counterexamples like HPV. This paper claims 'yes', but doesn't list any specific examples. Some mutagens might be more specific to genes involved in cell cycle regulation, so I could see how a weak mutagen is a powerful carcinogen.

My question is, can you go the other way? Are there mutagens that just do not cause cancer? If they do not exist or are not known to exist, are they even possible?

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Great question! – Christiaan Mar 10 '15 at 12:59
up vote 12 down vote accepted

All mutagens are potential carcinogens. Unless the mutagen is highly specific to a site.

HPV causes oncogenic transformation of a cell because of certain proteins that it expresses. Its mechanism is directed and specific. Most "carcinogens" are non-specific agents. However according to the definition, HPV can be called a carcinogen. Retroviruses can randomly integrate near an oncogene and cause oncogenic transformation (This is a mutation in principle. Not a point mutation though. They can also integrate within a gene and knock it out). Alcohol and estrogen are not carcinogens. A mutated estrogen receptor can lead to cancer. Estrogen is just a signal. Alcohol consumption for a very long time may perhaps play a role in carcinogenesis because of elevated levels of ROS but higher cancer incidence in alcoholics is not observed.

If you consider the new tools developed for site directed mutagenesis, such as ZFN, CRISPR-Cas and TALEN as mutagens then they are not carcinogenic. However the term mutagen is not used for these molecules. Mutagen almost always refers to a molecule that causes random mutagenesis thereby making it a carcinogen.

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ZFNs in particular fit quite neatly the counter-example I was looking for above. Good answer. – Resonating Jun 26 '14 at 19:49
Why do you claim that HPV is not carcinogenic? A quick google search on "HPV carcinogenesis" turns up multiple papers mentioning HPV induced carcinogenesis. – March Ho Mar 11 '15 at 6:36
@MarchHo HPV causes an oncogenic transformation and though it causes cancer the organism itself may not be called a carcinogen. Would an siRNA against p53 be called a carcinogen? Potentially yes. But the term carcinogen is used mostly for non-specific agents that increase the risk of cancer. I was too hard on that statement though; I'll edit it. – WYSIWYG Mar 11 '15 at 6:51
Can you provide a definition from a scientific paper/textbook that supports your nomenclature? I looked through a number of dictionaries (although not specifically geared to the field of oncology) and all of them defined "carcinogen" as "any substance which causes cancer". Furthermore, this paper seems to define carcinogens that cause cancer indirectly as "epigenetic carcinogens". Regarding your question, I would actually call such an siRNA carcinogenic. – March Ho Mar 11 '15 at 7:12
@MarchHo Unfortunately we don't have standard nomenclatures for many things in biology. I'll look up and let you know. Sometimes the published/commonly used/highly referenced nomenclature is misleading and erroneous. By definition any agent that causes or can possibly cause cancer is a carcinogen: that would include HPV and the p53-siRNA too. I don't know if this can be called a standard reference. – WYSIWYG Mar 11 '15 at 7:59

I'm no expert on the matter, but just quoting from Wikipedia:

Mutagens are not necessarily carcinogens, and vice versa. Sodium Azide for example may be mutagenic (and highly toxic), but it has not been shown to be carcinogenic.

It cites Toxicology And Carcinogenesis Studies Of Sodium Azide.

So it would appear the answer is no. Not all mutagens carcinogens.

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Sodium azide is only mutagenic part of the time(half of the strains tested), and there's this paper that shows that sodium azide isn't a mutagen in mammals. It's still poisonous (cerebral necrosis!) but neither a mutagen nor a carcinogen in mammals. – Resonating Jun 25 '14 at 16:02
It seems like there should be a counter-example (a mutagen with zero or negligible carcinogenicity) but I can't find one. – Resonating Jun 25 '14 at 16:04

protected by Christiaan Mar 12 '15 at 12:11

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