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.
Beamand
J A
JA
BIBRA Toxicology International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK.
Wield
P T
PT
Morin
C A
CA
Mistry
H
H
Davies
S
S
Price
R J
RJ
Lake
B G
BG