GENOTOXICITY OF N-NITROSO-N-METHYLUREA AND ACETONE OXIME IN THE TRANSGENIC DROSOPHILA CARRYING THE HUMAN GENE ENCODING A SUBUNIT OF GLUTATHIONE-S-TRANSFERASE

The genotoxic effects of N-nitroso-N-methylurea (MNU) and acetone oxim e (ACOX) were tested in the Somatic Mutation and Recombination Test (S MART) in Drosophila melanogaster. We have performed the same assay on transgenic flies expressing the human gene encoding a glutathione S-tr ansferase alpha subunit (HGST), The SMART assay is used here to demons trate genotoxicity and to determine the effect of human glutathione S- transferase on the genotoxic response, Three types of Drosophila strai ns were used: non-transgenic strains first described by Szabad (1986), transgenic strains derived from the Szabad strains but expressing the bacterial lacZ gene, and similarly derived transgenic strains express ing the HGST gene, MNU was highly genotoxic in both transgenic and non -transgenic flies. The non-transgenic flies were significantly more se nsitive to the genotoxic effects of MNU compared to both types of tran sgenic flies, There were statistically significant differences between the transgenic HGST crosses and transgenic lacZ and non-transgenic co ntrol crosses but there was no significant difference between the geno toxic response to MNU in flies from the transgenic cross with lacZ and from the cross carrying three copies of HGST. ACOX also proved to be genotoxic to both non-transgenic and transgenic flies. However, flies carrying three copies of the gene were significantly more resistant to the genotoxic effect of ACOX than those transgenic flies with two or no copies of the human gene.