Profiles of ethanol-induced microsomal alkoxyresorufin (alkoxyphenoxazone) O-dealkylation: comparison with phenobarbital- and Aroclor 1254-induced systems.
The O-dealkylation of various substituted alkoxyphenoxazones by liver microsomes from rats chronically fed ethanol is compared with that from pair-fed controls to determine whether there is any catalytic selectivity which could serve as an indicator for induction of cytochrome P-450j. Microsomes derived from animals pretreated with the better characterized inducers phenobarbital and Aroclor 1254 were also studied as positive controls. The specific activities (units/mg microsomal protein) but not the turnover numbers (units/nmol cytochrome P-450) were significantly increased by ethanol ingestion compared to pair-fed controls for methoxy-, ethoxy-, and pentoxy-resorufin O-dealkylation. Ethanol ingestion produced a significant increase in both specific activity and turnover number for the O-dealkylation of benzyloxy-resorufin. The degrees of induction of alkoxyresorufin-O-dealkylation activity measured for EtOH-induced microsomes range from 1.7 for methoxyresorufin to 4.8 for benzyloxyresorufin and are small in comparison to the values for phenobarbital and Aroclor 1254. This pattern of induction suggests that the minor isoforms induced by phenobarbital may be propagated by chronic ethanol ingestion.
Winston
G W
GW
Department of Biochemistry, Louisiana State University, Baton Rouge 70803.
Narayan
S
S
Bounds
P L
PL
D000437:Alcoholism / Q000201:enzymology*; D000818:Animals; D001140:Aroclors / Q000494:pharmacology*; D020111:Chlorodiphenyl (54% Chlorine); D019362:Cytochrome P-450 CYP2B1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D010088:Oxidoreductases / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D001140:Aroclors; D020111:Chlorodiphenyl (54% Chlorine); D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019362:Cytochrome P-450 CYP2B1; D010634:Phenobarbital