Salmonella test positive and negative carcinogens show different effects on intrachromosomal recombination in G2 cell cycle arrested yeast cells.

There is considerable controversy about the extrapolation of results obtained with high doses of chemicals in long-term and animal carcinogenesis studies to the low doses human beings are exposed to. In the present study, we compare the effect of Salmonella test positive carcinogens, ethyl methanesulfonate, methyl methanesulfonate, 4-nitroquinoline-1-oxide and gamma-rays versus Salmonella test negative carcinogens, benzene, safrole, urethane, thiourea and carbon tetrachloride over a dose range of 10(4)-fold on the frequency of intrachromosomal recombination in Saccharomyces cerevisiae. This short-term test is positive with both kinds of carcinogens. The Salmonella test negative carcinogens safrole, benzene and carbon tetrachloride induced intrachromosomal recombination to much higher levels in G2 arrested cells compared to growing cells; the reverse was true for the Salmonella test positive carcinogens. The Salmonella test positive carcinogens caused an almost linear dose response for induction of intrachromosomal recombination starting at a dose 100- to 1000-fold below the lowest toxic dose. In contrast, all Salmonella test negative carcinogens showed a sharp threshold below which no effect was detected, and the first effective dose for induction of intrachromosomal recombination was the first toxic dose.