INDUCTION OF MIXED-FUNCTION OXIDASE ACTIVITIES IN CYNOMOLGUS MONKEY HEPATOCYTE CULTURES

Previous work has demonstrated that primary rat hepatocyte cultures ma y 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 mon key 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 mu g Aroclor 1254/ml, 10 mu M beta-naphtho flavone (BNF), 2 mM phenobarbitone (PB) and 100 mu M Wy-14,643. All fo ur compounds induced 7-benzoxyresorufin O-debenzylase activity to 160- 280% of control levels, whereas 7-ethoxyresorufin O-deethylase activit y was induced by WY, PB, BNF and ARO to 165, 215, 605 and 1165% of con trol, respectively. These results demonstrate that cultured Cynomolgus monkey hepatocytes respond to some known enzyme inducers and hence ma y be useful for screening chemicals for induction of xenobiotic metabo lism in primate liver.