INDUCTION IN THE GENE RNR3 IN SACCHAROMYCES-CEREVISIAE UPON EXPOSURE TO DIFFERENT AGENTS RELATED TO CARCINOGENESIS

The induction of the gene RNR3 was investigated in yeast Saccharomyces cerevisiae using RNR3/lacZ fusion. Gene induction was monitored by me asuring beta-galactosidase activity. Various drugs that cause DNA dama ge effectively induced RNR3 expression; alkylating agents (cisplatin, mitomycin C and N-methyl-N'-nitro-N-nitrosoguanidine), a radical produ cer (bleomycin), and an intercalator (actinomycin D) induced RNR3. Whe n yeast expressing rat CYP1A1 was exposed to 2-aminofluorene, a concen tration-dependent induction of RNR3 was observed. Aflatoxin B-1 also i nduced the expression of RNR3 in the same yeast strain concomitant wit h inhibition of cell growth. In control yeast, no induction of RNR3 wa s observed upon exposure to 2-aminofluorene or aflatoxin B-1. Exposure to 2-acetylaminofluoren or benzo[a]pyrene did not lead to induction o f RNR3 in yeast expressing CYP1A1. These results indicate that DNA dam age by chemicals related to carcinogenesis induces RNR3, and that acti vation of these procarcinogens was required for DNA damage-dependent i nduction of RNR3.