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© 1986 Oxford University Press

other

Tumor-promoting activity of benzodiazepine tranquilizers, diazepam and oxazepam, in mouse liver

Bhalchandra A. Diwan, Jerry M. Rice and Jerrold M. Ward

Laboratory of Comparative Carcinogenesis, Division of Cancer Etiology, National Cancer Institute, National Institutes of Health Frederick, MD 21701–1013, USA

The widely used benzodiazepine tranquilizers diazepam and oxazepam promoted development of hepatocellular hyperplastic foci and hepatocellular neoplasms (adenomas and carcinomas) when they were fed in diet to male B6C3F1 mice after initiation by N-nitrosodiethylamine. Diazepam was more effective than oxazepam and its effect was proportionate to dose. Both diazepam and oxazepam induced hepatomegaly, cytochrome P-450 and cytochrome P-450-dependent amino-pyrine N-demethylase activity in hepatocytes, effects similar to those produced by a well-known rodent liver tumor promoter, phenobarbital. In view of the importance and widespread use of this class of compounds, more work is warranted to examine their effects on tumor development in different mammalian species.


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