Does it cause cancer?
Genetic vs. Epigenetic carcinogens.
The term genotoxic refers to chemicals that can damage the DNA of a cell - the cell's genome. We have already talked about mutations caused by adducts. There are hundreds of in vitro tests for genotoxicity. The Ames test is the oldest and best known. Here's some more about it. The test starts with the suspect mutagen being mixed with some activating agent, often microsomes, cofactors, oxygen and nutrients. After enough time for the activation to take place, the number of bacteria having mutations are measured. There are many variations on the basic tests, including different activation systems for particular types of chemicals. One issue with the Ames test is that there are often false positives. That is, chemicals cause mutations in these bacteria, but not in other types of cells or test systems. BUT, it turns out that's true with all the in vitro systems.
In the early days, the Ames test was taken by some as proof that a substance could cause cancer. This led to many misunderstandings, as common chemicals nutrients also tested positive. Dr. Ames never said his test was a positive test for the carcinogenic capacity of chemicals. And (perhaps out of embarrassment, I'm speculating) he has become a vocal advocate of a rational approach to the study of chemical carcinogens. Here is a brief news release about his work. We will read a more technical paper of his for homework: Ames on the causes of cancer.
Here's an international site of a commercial testing laboratory: Note the many tests for genetic toxicity they offer. Note that there are other forms of genetic toxicity that are not technically "mutations." For example Chromosome Aberrations: frank breakage of chromosomes (clastogensis), sister chromatid exchanges (SCE), micronuclei (a piece of DNA is cast out of the nucleus), Aneuploidy (missing copies of a chromosome) and so on. All may result is the same situation as a simple mutation in otherwise healthy DNA, incorrect proteins being produced by the cell or required proteins not being produced.
Besides bacterial cells, plant cells, fungi, and mammalian cells are used in other, vaguely similar, tests for genetic toxicity. The top half of this newsletter has a comparison of genotoxicity testing methods, although they discuss some thing we will cover under reproductive toxicology in a few weeks. Genotoxicty site.