This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Evarts, R. P. Articles by Brown, C. Search for Related Content PubMed PubMed Citation Articles by Evarts, R. P. Articles by Brown, C.

Pyrazole Effects on Mutagenicity and Toxicity of Dimethylnitrosamine in Wistar Rats

Laboratory of Carcinogen Metabolism, National Cancer Institute, Bethesda, Maryland 20205

¹ To whom requests for reprints should be addressed, National Cancer Institute, Bldg. 37, Room 3B27, Bethesda, Md. 20205.

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.

Received 4/ 5/82. Accepted 11/ 1/82.

This article has been cited by other articles:

				K. J. Woodcroft and R. F. Novak Xenobiotic-Enhanced Expression of Cytochromes P450 2E1 and 2B in Primary Cultured Rat Hepatocytes Drug Metab. Dispos., April 1, 1998; 26(4): 372 - 378. [Abstract] [Full Text]