Fundamental Toxicology

Genetic toxicology the study of toxic effects on the genetic material originated with the experiments of Muller (1927), who observed artificial transmutation of the gene by ionising radiation on the fruit fly, Drosophila melanogaster. The study of chemically induced mutation also has a long history, the first scientific publication by Auerbach et al. (1947), using Muller's fruit fly model, described mutations arising from exposure to sulfur mustards. Deep concern over mutagenesis was first expressed in the mid-1960s with the discovery of supermutagens , chemicals such as ICR-170, AF-2, hycanthone and ?-propriolactone that induce high levels of mutation at high levels of survival. Several leading geneticists were concerned that supermutagens might be widely distributed (Crow, 1968) either because they had passed through traditional toxi-ciry screens without showing adverse effects or because they had never been tested at all. In spite of these concerns, however, the major impetus given to mutagenesis as a branch of toxicology came from the belief that carcinogens could be predicted from assessment of their potential for interacting with DNA. Thus, Ames et al. (1973) pronounced carcinogens are mutagens . While this may have been the spark that became a blaze of activity in developing and validating new tests for genetic toxicity, the concern that the human germ line should be well protected in its own right also benefited. The result is that tests for genetic toxicity are used to identify potential human germ-line cell mutagens as well as in assessment of carcinogenicity and...