title: Recombinagenic activity of four compounds in the standard and high bioactivation crosses of Drosophila melanogaster in the wing spot test.
abstract: The wing somatic mutation and recombination test (SMART) using Drosophila melanogaster was employed to determine the recombinagenic and mutagenic activity of four chemicals in an in vivo eukaryotic system. Two different crosses involving the wing cell markers mwh and flr(3) were used: the standard cross and a high bioactivation cross. The high bioactivation cross is characterized by a high constitutive level of cytochromes P450 which leads to an increased sensitivity to a number of promutagens and procarcinogens. Three-day-old larvae derived from both crosses were treated chronically with the oxidizing agent potassium chromate and with the three procarcinogens cyclophosphamide, p-dimethylaminoazobenzene and 9,10-dimethylanthracene. From both crosses two types of progeny were obtained: marker-heterozygous and balancer-heterozygous. The wings of both genotypes were analysed for the occurrence of single and twin spots expressing the mwh and/or flr(3) mutant phenotypes. In the marker-heterozygous genotype the spots can be due either to mitotic recombination or to mutation. In contrast, in the balancer-heterozygous genotype only mutational events lead to spot formation, all recombination events being eliminated. The oxidizing agent potassium chromate was equally and highly genotoxic in both crosses. Surprisingly, the promutagen cyclophosphamide also showed equal genotoxicity in both crosses, whereas p-dimethylaminoazobenzene was negative in the standard cross, but clearly genotoxic in the high bioactivation cross. 9,10-Dimethylanthracene showed a rather weak genotoxicity in the high bioactivation cross. Analyses of the dose-response relationships for mwh clones recorded in the two wing genotypes demonstrated that all four compounds are recombinagenic. The fraction of all genotoxic events which are due to mitotic recombination ranged from 83% (9,10-dimethylanthracene) to 99% (p-dimethylaminoazobenzene). These results demonstrate that the wing spot test in Drosophila is most suited to the detection of recombinagenic activity of genotoxic chemicals.
authors.affiliation: Institute of Toxicology, Swiss Federal Institute of Technology (ETH) Zurich, CH-8603 Schwerzenbach, Switzerland.
authors.forename: M A
authors.initials: MA
authors.lastname: Spanó
authors.forename: H
authors.initials: H
authors.lastname: Frei
authors.forename: F E
authors.initials: FE
authors.lastname: Würgler
authors.forename: U
authors.initials: U
authors.lastname: Graf
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000633:toxicity; D001711:Biotransformation / Q000235:genetics; D002840:Chromates / Q000633:toxicity; D003433:Crosses, Genetic; D003520:Cyclophosphamide / Q000633:toxicity*; D004331:Drosophila melanogaster / Q000166:cytology / Q000187:drug effects / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000187:drug effects; D008297:Male; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000633:toxicity*; D016877:Oxidants / Q000633:toxicity; D017680:Potassium Compounds / Q000633:toxicity; D011995:Recombination, Genetic / Q000187:drug effects*; D014921:Wings, Animal / Q000166:cytology / Q000187:drug effects*; D004124:p-Dimethylaminoazobenzene / Q000633:toxicity*
chemical_list: D000873:Anthracenes; D002840:Chromates; D005819:Genetic Markers; D009153:Mutagens; D016877:Oxidants; D017680:Potassium Compounds; C027373:potassium chromate(VI); D003520:Cyclophosphamide; D004124:p-Dimethylaminoazobenzene; C029126:9,10-dimethylanthracene