Tumor-promoting activity of benzodiazepine tranquilizers, diazepam and oxazepam, in mouse liver.
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 aminopyrine 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.
B A
BA
Diwan
J M
JM
Rice
J M
JM
Ward
D000633:Aminopyrine N-Demethylase / Q000096:biosynthesis; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003043:Cocarcinogenesis; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D003975:Diazepam / Q000633:toxicity*; D004052:Diethylnitrosamine; D004790:Enzyme Induction / Q000187:drug effects; D008099:Liver / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D010076:Oxazepam / Q000633:toxicity*; D010634:Phenobarbital / Q000633:toxicity; D013997:Time Factors
D004052:Diethylnitrosamine; D010076:Oxazepam; D003577:Cytochrome P-450 Enzyme System; D000633:Aminopyrine N-Demethylase; D003975:Diazepam; D010634:Phenobarbital