The inhibitory effect of the fungicides captan and captafol on eukaryotic topoisomerases in vitro and lack of recombinagenic activity in the wing spot test of Drosophila melanogaster.
In studies on the mechanisms of mutagenic and carcinogenic action of captan and captafol-related chloroalkylthiocarboximide fungicides, two effects were tested: (i) the effect of both compounds on the activity of eukaryotic topoisomerases I and II in vitro, and (ii) their mutagenic and recombinagenic activity in the somatic mutation and recombination test (SMART) in wing cells of Drosophila melanogaster. Only captafol inhibited the activity of topoisomerase I (10-20% inhibition of activity in the range of 10-100microM). In contrast, both chemicals decreased the activity of topoisomerase II already at 1microM concentration (50 and 20% inhibition of activity by captafol and captan, respectively).Genotoxicity was tested in vivo by administrating both compounds by acute (3h) and chronic feeding (48h) of 3-day-old larvae. In acute feeding, captan and captafol demonstrated positive results only for small single and total spots in 10-100mM exposure concentration range. Both chemicals were inconclusive for large single spots, as well as for twin spots. In chronic treatment, captan showed positive results only for small single and total spots at 2.5 and 5mM concentrations. Captafol gave inconclusive results over all concentrations tested. The results of the acute treatment experiments which have been performed at very high doses (50% toxicity at higher doses) indicate very weak overall mutagenic activity of both test fungicides.
Department of Biochemistry, Medical University of Warsaw, ul. Banacha 1, Poland. ivrahden@amwaw.edu.pl
Iwonna
I
Rahden-Staron
D000818:Animals; D002215:Captan / Q000031:analogs & derivatives* / Q000633:toxicity*; D003433:Crosses, Genetic; D053138:Cyclohexenes; D004305:Dose-Response Relationship, Drug; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000633:toxicity*; D005260:Female; D005659:Fungicides, Industrial / Q000633:toxicity*; D066298:In Vitro Techniques; D007940:Leukemia L5178 / Q000201:enzymology; D008297:Male; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000633:toxicity*; D011995:Recombination, Genetic / Q000187:drug effects; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D014921:Wings, Animal / Q000187:drug effects
D053138:Cyclohexenes; D004791:Enzyme Inhibitors; D005659:Fungicides, Industrial; D009153:Mutagens; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; C001614:captafol; D002215:Captan