Mutations and Homologous Recombination Induced by N-Substituted Aryl Compounds in Mammalian Cells

Abstract

It is widely recognized that the transformation of normal cells into tumorigenic cells is a multistep process, and there is substantial evidence that mutations and gene rearrangements are involved in causing one or more of the required changes. However, the molecular mechanisms by which carcinogens induce such changes in mammalian cells are not well understood. We are making use of a shuttle vector, pZ189, containing a target gene, supF, to examine the frequency and kinds of mutations induced by a series of N-substituted aryl compounds and structurally-related carcinogens, as well as their specific location in the target gene (spectrum of mutations) (Yang et al., 1987; 1988; Mah et al., 1989). In these experiments, the plasmid is treated with radiolabeled carcinogens and allowed to replicate in the human cell line 293 where the mutations are introduced. The progeny plasmids are rescued, analyzed for mutated supF genes, and the kinds and spectra of mutations are determined in order to identify common features in the modes of action of the various agents and determine how they differ from each other.