How can the Ames test detect a human carcinogen?

Question

Using the Ames test, we add a mutagen to auxotrophic salmonella with mutations in the histidine pathway and rat liver extract to simulate metabolism. How would we know if the carcinogen is a human carcinogen or not?

I'm guessing that if a mutagen showed no growth without the rat liver extract, but then growth with the rat liver extract this would mean that it is a human carcinogen. Is this true?

Answer 1

The Ames test aims to find out if a chemical (not yet known to be mutagen) is indeed a mutagen, either directly, or following treatment with liver enzymes (which may metabolise a chemical to mutagenic derivatives during "detoxification"). As you explain, the test involves looking for reversion of various histidine auxotrophic strains of Salmonella.

If the chemical is found to mutagenic in the Ames test then there is a good chance that it will be a carcinogen because of the link between mutagenesis and cancer. In practice further unrelated tests are needed to eliminate false positives.

In this review of the method

Mortelmans & Zeiger (2000) The Ames Salmonella/microsome mutagenicity assay. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 455: 29-60

the authors state that:

...there is a high predictivity of a positive mutagenic response in the Ames test for rodent carcinogenicity...ranging from 90% to 77%...