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 flr3 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.
Inoue
H
H
Toxicology Laboratory, Yokohama Research Center, Mitsubishi Chemical Corporation, Kanagawa, Japan.
Baba
H
H
Awano
K
K
Yoshikawa
K
K
D000818:Animals; D003434:Crossing Over, Genetic; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004331:Drosophila melanogaster / Q000187:drug effects / Q000235:genetics*; D005260:Female; D005298:Fertility; D017344:Genes, Insect; D006118:Griseofulvin / Q000633:toxicity*; D006579:Heterozygote; D007814:Larva; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation
D009153:Mutagens; D006118:Griseofulvin