Differences in teratogenic and toxic properties of alcohol dehydrogenase inhibitors pyrazole and 4-methylpyrazole in Drosophila melanogaster: I. ADH allozymes in variable genetic backgrounds.
Pyrazole and 4-methylpyrazole (4-MP) are effective inhibitors of alcohol dehydrogenase (ADH) activity in mammals both in vivo and in vitro. 4-MP has a tenfold higher inhibition specificity compared with pyrazole. Pyrazole proved a teratogenic compound in Drosophila melanogaster. Treatment of third instar larvae of D. melanogaster with pyrazole, in contrast with 4-MP, produced an increase in the number of dorsocentral and scutellar macrochaetae and wing-notches in the adult fly. A large difference in the penetrance of terata in males and females was observed. Similar effects were observed in flies lacking ADH molecules. The teratogenicity of pyrazole must be due to disturbance of processes other than ADH inhibition. Synergistic effects were observed between pyrazole and methoxyacetic acid (MAA), an in vitro inhibitor of sarcosine dehydrogenase activity. Each of these compounds, when fed to early third instar larvae, produced terata resembling the Notch mutant of D. melanogaster.
Eisses
K T
KT
Department of Plant Ecology and Evolutionary Biology, Utrecht University, The Netherlands.
D000085:Acetates / Q000633:toxicity*; D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors*; D000818:Animals; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D004357:Drug Synergism; D005260:Female; D000077604:Fomepizole; D007814:Larva / Q000187:drug effects; D008297:Male; D011720:Pyrazoles / Q000633:toxicity*
D000085:Acetates; D011720:Pyrazoles; C031280:pyrazole; D000077604:Fomepizole; D000426:Alcohol Dehydrogenase; C013598:methoxyacetic acid