Studies on metabolic activation of vinyl chloride in Drosophila melanogaster after pretreatment with phenobarbital and polychlorinated biphenyls.
It is known that vinyl chloride is metabolized by the mixed function oxygenase system in the liver to reactive mutagenic and carcinogenic metabolites. This metabolic activation was studied in Drosophila melanogaster by measuring the uptake of 14C from labelled vinyl chloride in different strains and with different pretreatments with phenobarbital and polychlorinated biphenyl (PCB) Clophen A50), well known inducers of cytochrome P-450. In accordance with previously obtained data on vinyl chloride induced sex linked recessive lethals, it was shown that pretreatment with inducers increased the uptake of labelled compound up to ten times. There was, however, a marked difference in response between the five strains used. In particular, the strain Hikone, known to be resistant to insecticides, had a comparatively high initial radioactivity from vinyl chloride without any pretreatment, but it was not or insignificantly inducible with phenobarbital or PCB. Crosses between Hikone and an inducible strain indicated essentially a dominance for the Hikone genotype. Tests on inducible strains showed the same response to phenobarbital by 2 h old larvae and adult male and females. Dimethylsulphoxide (DMSO) used as a solvent decreased both the initial uptake of 14C and particularly the induction by PCB. The use of Tween 80 as an emulsifier did not have such an effect. It is emphasized that the interstrain variation in metabolic activation and inducability has to be taken into consideration in order to optimize the use of Drosophila for mutagenicity testing. This variation also opens up new possibilities of analyzing the mixed function oxygenase system biochemically and genetically.
D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D004331:Drosophila melanogaster / Q000187:drug effects / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology*; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D012737:Sex Factors; D013045:Species Specificity; D014752:Vinyl Chloride / Q000378:metabolism*; D014753:Vinyl Compounds / Q000378:metabolism*
D014753:Vinyl Compounds; D011078:Polychlorinated Biphenyls; D014752:Vinyl Chloride; D010634:Phenobarbital