ABSTRACT
This chapter considers the known basic biological mechanisms of the induction of chemical carcinogenesis and then discusses on a tissue-by-tissue basis how the available information fits the presently available mechanistic knowledge. It is possible to define a carcinogen as “an agent that leads to a statistically significant increase in the number of benign and/or malignant tumors in a tissue”. Short-term in vitro and in vivo genotoxicity tests, such as the Ames Salmonella typhimurium assay, have proved singularly successful for identifying electrophile-generating carcinogens. The ability of certain substances to lead to the formation of oxidation products of DNA has recently begun to attract considerable attention. Fat metabolism provides a convenient approach to this topic. Scientists working for Imperial Chemical Industries Ltd. in England identified a receptor protein of the steroid hormone receptor superfamily involved in the mechanism of action of peroxisome-proliferating chemicals. Dose is a centrally important concept in both toxicology and carcinogenesis.
