Does it cause cancer?
Too Many Rodent Carcinogens
A larger problem lurks in the nature of the animal testing. We have a readable technical article by Ames and Gold, two Berkeley scientists who are pioneers in molecular biology and cancer research, who are part of a research center funded by the National Institute of Health, NIEHS Center for Environmental Health Sciences. Go to Course Documents and download the pdf file. Read it carefully, and save it for homework. (A few words are defined in a glossary below.)
The article, written in 1990, is pivotal in the field of environmental health. In the US, the NEPA and other nationwide environmental legislation, started around 1970. The 1970's era legislation dealt with gross environmental pollution and hazards such as raw sewage dumped into streams and skies darkened by pollution from smokestacks. In the 1980's there was a vast increase in environmental laws, many dealing with "cancer-causing chemicals" in the environment. This legislation and regulations were based on the assumption that there were no "safe" or properly put, no risk-free exposure to chemicals that had been proven to cause cancer in animals. That is, there was no "threshold" for the carcinogenic response. From what you have learned so far, you should see some logic in that. Certain chemicals (and other agents, like radiation) cause mutations, and enough mutations cause cancer. Therefore anything that can cause a mutation could cause cancer, or at least contribute to it. You also realize that with the slope factor approach, it is always possible to calculate a cancer incidence based on any concentration of a chemical, no matter how low.
Many chemicals were tested. Ames and Gold discuss three assumptions of the 70's that were found lacking: "a) only a small proportion of chemicals would have carcinogenic potential, b) testing at high dose would not produce a carcinogenic effect unique to the high dose and c) chemical carcinogenesis would be explained by the mutagenic potential of chemicals. However, it seems time to take account of new information suggesting that all three assumptions are wrong. "
For your homework, read the article carefully and discuss in three or four paragraphs what evidence Ames and Gold present that assumptions b.) and c.) were wrong, and how does this affect the assumption about a threshold for carcinogens.
A glossary:
histones. Histones are structural proteins that support DNA
Heterozygous and Homozygous. Heterozygous means there are two copies of gene, maternal and paternal, in cell. Homozygous means there is only one copy. So an agent that destroys a gene on one chromosome can change a cell from heterozygous to homozygous for that gene. This is especially important for genes like tumor suppressor genes where both copies would need to be knocked out to breach a cell's defense.
" 5-methyl C" and Methylation. DNA has 4 nucleotides, A, T, G, and C. There are variants of A and C whereby a methyl group is attached, although only the methylated-C is important in vertebrates. Although only a small percentage of C is methylated, these sites are important in switching gene expression on an off, and in repairing DNA.
quiescent (not normally replicating) tissues. Some tissues, such as the lining of the GI tract or the skin, are constantly being shed and replaced by cellular replication. In immature life stages, almost all tissues are growing. In adults most tissues are quiescent, not replicating, for example the liver is quiescent, unless it is disturbed or damaged.
Here is another Ames and Gold article you may find interesting, but do not need to read now.