Induction of cytochrome P-448 isozyme(s) in primary cultured rat hepatocytes by drugs which induce different isozymes in vivo.
Effect of 2-methoxy-4-aminoazobenzene (2-MeO-AAB) and 3-methylcholanthrene (MC) on the induction of microsomal cytochrome P-448 isozymes in primary cultured rat hepatocytes was examined by means of immunochemical methods such as protein A-enzyme-linked immonosorbent assay and immuno-blots using anti-rat cytochrome P-448 monoclonal antibodies and by means of bacterial mutation tests. Although 2-MeO-AAB selectively induced cytochrome P-448H and MC induced both cytochrome P-448H and a low spin form of cytochrome P-448 (P-448L) in the liver of rats, addition of these chemicals to primary cultured rat hepatocytes resulted in selective induction of cytochrome P-448L, as determined by the immunological methods. This was substantiated by the bacterial mutation test using Salmonella typhimurium TA 98 bacteria and two aromatic amine substrates with different specificities to the cytochrome P-448 isozymes. These results suggest that the responses of rat hepatocytes to cytochrome P-450 inducers are different in in vivo and in vitro.
Hishinuma
T
T
Department of Hygienic Chemistry, Tohoku University, Sendai, Japan.
Degawa
M
M
Masuko
T
T
Hashimoto
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal; D001391:Azo Compounds / Q000494:pharmacology*; D002478:Cells, Cultured; D019388:Cytochrome P-450 CYP1A2; D003580:Cytochromes / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D007163:Immunosorbent Techniques; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008748:Methylcholanthrene / Q000494:pharmacology; D051381:Rats; D010128:p-Aminoazobenzene / Q000031:analogs & derivatives / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D001391:Azo Compounds; D003580:Cytochromes; D007527:Isoenzymes; C053767:2-methoxy-4-aminoazobenzene; D008748:Methylcholanthrene; D010128:p-Aminoazobenzene; C017170:Cyp1a2 protein, rat; D019388:Cytochrome P-450 CYP1A2