Premium
Ethanol‐Inducible Cytochrome P‐450: Assessment of Substrates' Specific Chemical Probes in Rat Liver Microsomes
Author(s) -
Lucas D.,
Berthou F.,
Dreano Y.,
Floch H. H.,
Menez J. F.
Publication year - 1990
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1990.tb01207.x
Subject(s) - microsome , hydroxylation , chemistry , cytochrome , ethanol , phenobarbital , demethylation , xenobiotic , cytochrome p450 , alcohol , acetone , microsoma , butanol , biochemistry , chromatography , metabolism , enzyme , endocrinology , biology , gene expression , gene , dna methylation
The capacity of liver microsomes to oxidize various substrates known to be specific of alcohol‐inducible cytochrome P‐450 was studied in rats treated with different xenobiotics such as 3‐methyl‐cholanthrene, phenobarbital, acetone, and ethanol. Analysis of results showed a significantly marked increase following ethanol and acetone treatments of the p ‐nitrophenol hydroxylation (283 ± 19% and 304 ± 21%), N ‐nitrosodimethylamine (NDMA) demethylation (280 ± 105% and 228 ± 95%), benzene hydroxylation (258 ± 60% and 236 ± 61%), butanol oxidation (173 ± 34% and 154 ± 32%), aniline hydroxylation (147 ± 22% and 95 ± 8%), and ether de‐ethylation (95 ± 17% and 83 ± 17%) and a not significant increase of N‐nitrosodiethylamine (NDEA) de‐ethylation (34 ± 11% and 9 ± 8%) in rat microsomes, respectively, versus control animals (mean ± SD, values expressed as nmol/min/nmole P‐450). All of these activities significantly decreased after 3‐MC treatment, except for the p ‐nitrophenol hydroxylation. PB treatment markedly enhanced NDEA de‐ethylation, p ‐nitrophenol, and benzene hydroxylations (106 ± 38%, 109 ± 14%, and 153 ± 62%, respectively) versus controls. These results suggest that NDMA and especially 1‐butanol are the most specific and useful probes of alcohol‐inducible cytochrome P‐450 in crude liver microsomes.