The Mutagenicity of Chemical Carcinogens: Correlations, Problems, and Interpretations

Abstract

Mutagenesis and carcinogenesis are complex cellular processes which are grossly similar in that each produces heritable changes in phenotype. Experimental mutagenesis by a pure chemical agent was first achieved by Auerbach and Robson (1944, 1946) and a variety of such agents are now known. Their mechanisms of action appear to be fairly well understood as consisting of expressible heritable changes in the molecular structure of the genetic material or DNA (Orgel, 1965; Freese and Freese, 1966; Auerbach, 1967; Freese, this book). Carcinogenesis by chemical agents was discovered first in humans almost 200 years ago, and today nearly a dozen agents active in the human and of widely varying structure are known (Clayson, 1962; Hueper and Conway, 1964; Miller, J. A., 1970). The experimental induction of cancer with a pure chemical compound was first achieved about 1930, and many chemical carcinogens of greatly differing structures are known today (see preceding references). However, it is not known at the molecular level how any chemical carcinogen induces the formation of cells which are not responsive to the growth controls of the host and which form neoplasms that grow more or less continuously and may invade normal tissues. This is also true of the carcinogenic action of viruses and radiation. Likewise, the molecular phenotype of no neoplasm is even partially understood.