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.