The role of specific cytochromes P450 in the formation of 7,12-dimethylbenz(a)anthracene-protein adducts in rat liver microsomes in vitro.

Abstract:

:The role of specific cytochrome P450 (P450) isoforms in the formation of adducts of 7,12-dimethylbenz(a)anthracene metabolites and membrane proteins has been investigated in vitro with microsomal fractions prepared from rats pretreated with various isoenzyme selective inducers. The effects of isoenzyme selective inhibitors were also evaluated. Adduct formation was shown to be mediated by P450 catalysed reactions but was unaltered, relative to untreated animals, in membranes from pyrazole- and clofibrate-treated animals suggesting that CYP2E1 and CYP4A1 are not involved in this process. However, adduct formation was significantly increased in microsomes from Sudan III-, phenobarbital- and dexamethasone-treated rats, suggesting the involvement of the CYP1A, CYP2B and CYP3A subfamilies, respectively. These conclusions were further supported by the finding that adduct formation in these microsomes could be inhibited by the isoenzyme-selective inhibitors alpha-naphthoflavone, metyrapone and troleandomycin, respectively.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Lambard SE,Burnett AK,Wolf CR,Craft JA

doi

10.1016/0006-2952(91)90421-z

subject

Has Abstract

pub_date

1991-09-27 00:00:00

pages

1529-35

issue

8

eissn

0006-2952

issn

1873-2968

pii

0006-2952(91)90421-Z

journal_volume

42

pub_type

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