Effects of Salmonella assay negative and positive carcinogens on intrachromosomal recombination in G1-arrested yeast cells

Abstract

A wide variety of carcinogens including Ames assay (Salmonella) positive as well as Salmonella-negative carcinogens induce intrachromosomal recombination (DEL recombination) in strain RS112 of Saccharomyces cerevisiae. It has been previously shown that the Salmonella-positive carcinogens ethyl methanesulfonate (EMS), methyl methanesulfonate (MMS) and 4-nitroquinoline-N-oxide (4-NQO) and the Salmonella-negative carcinogens safrole, benzene, thiourea, carbon tetrachloride and urethane induce DEL recombination in G₂-arrested yeast cells. DEL recombination is preferentially induced by safrole, benzene and carbon tetrachloride in G₂-arrested cells which might be explained by preferential induction of unequal sister chromatid recombination leading to deletions. To test this, cells of strain RS112 were arrested in the G₁ phase of the cell cycle, exposed to these carcinogens and the frequencies of DEL and interchromosomal recombination (ICR) were determined. EMS, MMS and 4-NQO induced DEL recombination and ICR in G₁-arrested cells with a linear dose-response curve. In contrast, the Salmonella-negative carcinogens safrole, benzene, carbon tetrachloride, thiourea and urethane induced DEL recombination and ICR with a threshold below which no significant increase was seen and only at already cytotoxic doses. EMS, MMS and 4-NQO were more recombinagenic in previous experiments with growing cells than in G₁-arrested cells. On the other hand, safrole, benzene and carbon tetrachloride were more recombinagenic in G₁-arrested than in growing cells. Thus, inducibility of DEL recombination in G₁-arrested cells parallels inducibility in G₂-arrested cells making it less likely that sister chromatid recombination events might be involved. These data are discussed in terms of the mechanism of induced DEL recombination and the possible biological activities of these carcinogens.