GENOTOXIC EFFECT OF GRISEOFULVIN IN SOMATIC-CELLS OF DROSOPHILA-MELANOGASTER

Griseofulvin (GF), a carcinogenic spindle poison, was tested in two types of somatic-cell assays of Drosophila melanogaster, one of which detects the induction of DNA damage and the other mutation/mitotic recombination. In both assays, GF was fed to tester larvae and genetic endpoints examined after emergence. In the wing spot test, trans-heterozygous flies carrying mwh and flr(3) wing-hair mutations produced both significant and dose-dependent increases in the frequency of mwh single spots over the control level but no increase of twin spots. In the DNA repair test, double-mutant larvae carrying both mei-9(a) (excision repair-defective) and mei-41(D5) (postreplication repair-defective) mutations showed hypersensitivity to killing by GF compared with their DNA repair-proficient counterparts, suggesting that GF caused potentially lethal DNA damages which were efficiently repaired by the DNA repair-proficient but not -defective larvae. These lines of evidence clearly demonstrate that GF is genotoxic in somatic cells of Drosophila. It is noted that (1) GF-fed larvae showed a developmental delay and (2) surviving adult flies had morphological abnormalities in their eyes and wings.