Genetic mode of action of cocarcinogens and tumor promoters in yeast and mice.

In experiments with yeast, cocarcinogens were found to be comutagenic and antirecombinogenic , tumor promoters to be corecombinogenic and antimutagenic. Substances that were cocarcinogens as well as tumor promoters had an intermediary effect. These results were confirmed in the mammalian spot test: By in vivo treatment of mice with the cocarcinogen catechol and the tumor promoter limonene carcinogen-induced recombination due to mitotic crossing over and gene mutations was reduced and enhanced, respectively. Our results support the hypothesis that mutagenesis is the mechanism by which chemicals induce malignancy, and that cocarcinogens modify the process by enhancement of mutagenicity whereas tumor promoters effect carcinogenesis by increase of the spontaneous frequency of recombination. In addition, induced mitotic recombination in mammals in vivo has been demonstrated for the first time.