Pyrazole effects on mutagenicity and toxicity of dimethylnitrosamine in Wistar rats.
The correlation between the in vivo toxicity and in vitro mutagenicity of dimethylnitrosamine and the activity of dimethylnitrosamine demethylase I (DMND I) after pyrazole treatment of rats was studied. The biological effects of pyrazole were measured either as toxicity to the rats or as mutations to Salmonella TA 92. A dose-response relationship was observed between DMND I activity and the administered dose of pyrazole. Pyrazole administration increased the toxicity of dimethylnitrosamine when measured as a 50% lethal dose or as a histopathological effect on the liver. Phenobarbital and methylcholanthrene administration did not have any effect on the activity of DMND I or on the number of histidine-revertant colonies when tested using the liquid suspension method in the presence of dimethylnitrosamine and the reduced nicotinamide adenine denucleotide phosphate-generating system. When microsomes from the pyrazole-treated animals were used in the mutagenesis assay, there was a linear correlation between DMND I activity and the number of histidine-revertant colonies. It is concluded that pyrazole treatment of animals increases the activity of liver DMND I, the toxicity of dimethylnitrosamine, and the number of mutations.
D000818:Animals; D004128:Dimethylnitrosamine / Q000494:pharmacology* / Q000633:toxicity; D007928:Lethal Dose 50; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009152:Mutagenicity Tests; D009154:Mutation; D011506:Proteins / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D011506:Proteins; D011720:Pyrazoles; C031280:pyrazole; D004128:Dimethylnitrosamine