On the Mechanism of Hepatocarcinogenesis of Benzodiazepines: Evidence that Diazepam and Oxazepam are CYP2B Inducers in Rats, and both CYP2B and CYP4A Inducers in Mice

Abstract

The aim of this study was to evaluate diazepam and oxazepam as cytochrome P450 inducers at doses previously shown to cause liver tumors in mice but not rats. In rats, diazepam and oxazepam induced CYP2B, and were as effective as phenobarbital despite lacking phenobarbital's tumor-promoting effect in rats. In mice, diazepam and oxazepam induced both CYP2B and CYP4A at dietary doses associated with liver tumor formation. It remains to be determined why diazepam and oxazepam induce CYP4A in mice but not rats and whether this difference accounts for the apparent species difference in the tumor-promoting activity of diazepam and oxazepam.

Key Words :

• Oxazepam
• Diazepam
• Phenobarbital
• CYP2B
• CYP4A
• Induction
• Tumor promotion
• Benzodiazepines