Regulation of cytochrome P-450 isozymes CYP1A1, CYP1A2 and CYP2B10 by three benzodioxole compounds.
Three benzodioxole (BD) compounds were used to investigate the structural requirement for regulation of the cytochrome P450 isozymes, CYP1A1, CYP1A2 and CYP2B10, in mouse liver. Male mice (C57BL/6) were treated intraperitoneally for 3 days with 5-t-butyl-1,3-benzodioxole (t-BBD), 5-n-butyl-1,3-benzodioxole (n-BBD) and 5-(3-oxobutyl)-1,3-benzodioxole (o-BBD). t-BBD-induced liver microsomes showed the highest pentoxyresorufin O-dealkylation (PROD) activity, while o-BBD induced microsomes showed slightly higher activity in ethoxyresorufin O-deethylation (EROD), benzo[a]pyrene hydroxylation (BaP-OH) and acetanilide hydroxylation (Acet-OH) assays. In vitro enzyme inhibition assays showed that n-BBD inhibited EROD and Acet-OH activities more than either o-BBD or t-BBD, while PROD activity was evenly inhibited by all three compounds. Western and northern blots showed that CYP1A1 was not detectably induced by any of the three BD compounds. The levels of CYP1A2 protein and mRNA were increased in all three treated livers. In addition to CYP1A2 induction, t-BBD also induced the protein and mRNA for CYP2B10.
Ryu
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DY
Department of Toxicology, North Carolina State University, Raleigh 27695, USA.
Levi
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PE
Hodgson
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D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D019388:Cytochrome P-450 CYP1A2; D019362:Cytochrome P-450 CYP2B1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D004149:Dioxoles / Q000494:pharmacology*; D015870:Gene Expression; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000201:enzymology; D008969:Molecular Sequence Data; D010088:Oxidoreductases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics
D017931:DNA Primers; D004149:Dioxoles; D007527:Isoenzymes; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019388:Cytochrome P-450 CYP1A2; D019362:Cytochrome P-450 CYP2B1