Induction of mixed function oxidase activities in Cynomolgus monkey hepatocyte cultures

Previous work has demonstrated that primary rat hepatocyte cultures may be used to screen compounds for induction of xenobiotic-metabolizing enzyme activities. In this study we have examined the effect of some known enzyme inducers in cynomolgus monkey hepatocytes. Cynomolgus monkey hepatocytes were isolated by a wedge perfusion technique and could be cultured in RPMI 1640 medium for at least 5 days. Hepatocytes were cultured for 70 hr with 10 mug Aroclor 1254/ml, 10 mum beta-naphthoflavone (BNF), 2 mm phenobarbitone (PB) and 100 mum Wy-14,643. All four compounds induced 7-benzoxyresorufin O-debenzylase activity to 160-280% of control levels, whereas 7-ethoxyresorufin O-deethylase activity was induced by WY, PB, BNF and ARO to 165, 215, 605 and 1165% of control, respectively. These results demonstrate that cultured Cynomolgus monkey hepatocytes respond to some known enzyme inducers and hence may be useful for screening chemicals for induction of xenobiotic metabolism in primate liver.