Question

Describe how the Ames test screens for potential environmental mutagens. Why is it thought that a compound that tests positively in the Ames test may also be carcinogenic?

Short answer

Describe the Ames test and explain why a compound testing positive in the Ames test is considered potentially carcinogenic. The Ames test is a biological assay that assesses the mutagenic potential of chemical compounds by examining their ability to revert mutated Salmonella typhimurium strains to their histidine-synthesizing wild type form. A compound that tests positive in the Ames test may be considered potentially carcinogenic because many carcinogenic substances can induce genetic mutations in the DNA of cells, which can lead to uncontrolled cell growth and tumor formation. However, a positive result in the Ames test does not guarantee a compound presents carcinogenic risk to humans, and further tests are needed to confirm this.

Step-by-step solution

Background on the Ames test

The Ames test is a biological assay used to screen for potential environmental mutagens, which are substances that can induce genetic mutations. Developed by Bruce Ames in 1973, the test measures the ability of a chemical compound to revert specific mutated strains of the bacterium Salmonella typhimurium back to their wild type form. These revertants are then able to synthesize the amino acid histidine, which is essential for their growth.

The Ames test process

The Ames test starts with a mutant strain of Salmonella typhimurium that is unable to synthesize histidine due to certain mutations in its DNA. The bacteria is then exposed to a test compound to screen for potential mutagenicity. The procedure can be broken down into the following steps: 1. Mix the test compound with the mutant bacteria and a substance that mimics mammalian metabolic activation (usually rat liver extract) in a test tube. 2. Spread the mixture onto a solid agar plate containing a little amount of histidine, which supports the bacteria's initial growth but is insufficient for long-term survival. 3. Incubate the plate for 48 hours to allow bacterial growth. 4. Observe the number of bacterial colonies that revert back to their wild type, which can synthesize histidine and thus survive on the agar plate. The greater the number of revertant colonies, the stronger the evidence of the test compound's mutagenic potential.

Connecting Ames test results to carcinogenicity

A compound that tests positive in the Ames test, meaning it causes a significant increase in the number of revertant colonies, may also be potentially carcinogenic. This is because many carcinogenic substances exert their effect by inducing genetic mutations in the DNA of cells, which could lead to uncontrolled cell growth and eventually the formation of tumors. Since the Ames test detects substances that can cause genetic mutations in bacteria, it's considered a useful indicator for assessing the potential cancer risk of environmental chemicals. However, it's important to note that a positive result in the Ames test doesn't guarantee a compound presents carcinogenic risk to humans and further tests are needed to confirm this. Conversely, it's possible for some non-carcinogenic compounds to also test positive in the Ames test due to their mutagenic activity. In summary, the Ames test screens for potential environmental mutagens by evaluating the ability of a test compound to revert mutated Salmonella typhimurium strains to their histidine-synthesizing wild type form. A compound with a positive result in the Ames test may be considered potentially carcinogenic because mutagenic substances can often induce genetic mutations that can lead to uncontrolled cell growth and the formation of tumors.