Differential stabilization of cytochrome P-450 isoenzymes in primary cultures of adult rat liver parenchymal cells.
Cytochrome P-450 dependent hydroxylation of testosterone was measured in 7-day-old cultures of primary rat liver parenchymal cells. Determinations were carried out in monocultures of parenchymal cells and co-cultures of parenchymal cells with rat liver nonparenchymal epithelial cells, or mouse embryo fibroblasts. In the monoculture system, testosterone metabolism was drastically reduced and hardly measurable after 7 days in culture. In the co-culture systems, individual P-450 isoenzymes were stabilized on different levels. P-450s p and presumably c were well preserved, P-450 a was reduced but clearly measurable, P-450 h was totally lost whereas P-450s b and e were not measurable after 7 days (the activities of these isoenzymes however were already low in freshly isolated parenchymal cells). The results were independent of the cell line used for co-cultivation and of the method of parenchymal cell isolation, that is whether collagenase or EDTA was used as the agent for dissociating the cells from the liver. The results showed that the co-cultivation of liver parenchymal cells with other nonparenchymal cells significantly improved the differentiated status of the former. In this cell culture system however, not every parameter was equally well stabilized.
Utesch
D
D
Institute of Toxicology, University of Mainz, Germany.
Molitor
E
E
Platt
K L
KL
Oesch
F
F
D000818:Animals; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism* / Q000502:physiology; D004622:Embryo, Mammalian / Q000166:cytology; D004795:Enzyme Stability; D005347:Fibroblasts / Q000166:cytology; D006900:Hydroxylation; D007527:Isoenzymes / Q000378:metabolism*; D008099:Liver / Q000166:cytology* / Q000201:enzymology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D051381:Rats; D011919:Rats, Inbred Strains; D013739:Testosterone / Q000378:metabolism
D007527:Isoenzymes; D013739:Testosterone; D003577:Cytochrome P-450 Enzyme System