Interaction of chemical carcinogens and drug-metabolizing enzymes in primary cultures of hepatic cells from the rat.
The experiments described in this paper have demonstrated that hepatocytes cultured on floating collagen membranes for periods of 10 days retain their ability to respond to the inducers of drug-metabolizing enzymes, phenobarbital and methylcholanthrene, by increases in cytochromes of the cytochrome P-450 complex. Since the regulation of these cytochromes is the rate-controlling factor in the metabolism of drugs and carcinogens in hepatocytes, such experiments indicate that hepatocytes cultured on floating collagen membranes retain those functions of the liver cell responsible for the metabolism and "activation" of carcinogenic substances. The data support this hypothesis and further indicate that this system may have potential application both in the investigation of hepatocarcinogenesis by chemicals in vitro and as a screening system for the detection of substances truly carcinogenic for the mammalian organism.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology*; D002478:Cells, Cultured; D003094:Collagen; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004260:DNA Repair / Q000187:drug effects; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D004798:Enzymes / Q000494:pharmacology*; D005260:Female; D006854:Hydrocortisone / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D008566:Membranes; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology; D010634:Phenobarbital / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D014444:Tyrosine Transaminase / Q000378:metabolism
D002273:Carcinogens; D004798:Enzymes; D008748:Methylcholanthrene; D003094:Collagen; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D014444:Tyrosine Transaminase; D006854:Hydrocortisone; D010634:Phenobarbital