The Ames Test. A geneticist named Bruce Ames devised a remarkably effective test that is cheap and fast, based on measuring mutation rates in the bacterium Salmonella typhimurium.

Ames selected two Salmonella strains to test. Both are mutant in that they can't make their own histidine and therefore require histidine in their growth medium. The assay is for "reversion" of the histidine requirement. This makes it possible to measure very rare events (rare his+ cells in a culture can form colonies when put on plates without histidine.

1. Strain one has a single nucleotide changed and reverts to his+ by single nucleotide changes that restore protein function.

2. Strain two has a single base frameshift mutation and reverts to his+ only when a restoring frameshift mutation occurs.

These two strains permit the detection of nearly all types of mutagenesis.

A basic problem that Ames solved is the fact that our liver cells are very active both in detoxifying mutagens and in altering harmless compounds to forms that are mutagenic (by mistake of course). Salmonella does not have these activities.

1. The solution is to pretreat the suspected mutagen to be tested with a rat liver extract, which carries out the liver-mediated (for example, Cytochrome P450 and FMO) changes.

2. This treated solution is then tested for inducing reversion to his+ in the two mutant Salmonella strains.

The Ames test is fairly reliable in giving a first estimate of carcinogenic capacity of compounds and is typically used as a first level test for new drugs, etc.