Induction of mitotic gene conversion with nitrous acid, 1-methyl-3-nitro-1-nitrosoguanidine and other alkylating agents in Saccharomyces cerevisiae

Abstract

1. Mitotic gene conversion was induced at three different hetero-allelic loci of the yeast Saccharomyces cerevisiae with nitrous acid, 1-methyl-3-nitro-1-nitrosoguanidine, N-nitroso-N-methylurethane, 1-nitroso-imidazolidone-2 and N-nitroso-N-methylcaproamide. 2. All agents were already able to induce mitotic gene conversion at very high frequencies (1×10-3 and more) at doses of low toxicity. 3. Induced mitotic gene conversion occurs in normal mitotic cells and does not result from a meiosis-like condition. 4. Mitotic gene conversion can be accomplished in non-dividing cells provided a certain degree of metabolic activity is possible. An entire DNA replication cycle, however, is not required. 5. Chemically induced mitotic gene conversion occurs as a process with localized effects. There is, however, a certain coincidence between conversional events and recombination in the near vicinity. Moreover, chemically induced gene conversion too is a non-reciprocal process. 6. Mitotic gene conversion is a biologically relevant process in diploids as it generates specific genetic alterations at much higher frequencies than do mutation or mitotic recombination especially in the case of heterozygosis due to multiple allelism. 7. It is pointed out that mitotic gene conversion possibly is common in all diploid organism. Moreover, one well analysed example of genetically determined tumorous growth in intraspecies hybrids in the genus Nicotiana is most readily explained by mitotic gene conversion. Further, mitotic gene conversion of spontaneous or induced origin is discussed as an important genetic process leading to cancer or to other diseases in man.