Induction, activation, and inhibition of hamster and rat liver microsomal arylamide and arylamine N-hydroxylase.
Cancer Res
; 40(10): 3540-6, 1980 Oct.
Article
em En
| MEDLINE
| ID: mdl-7438040
ABSTRACT
By applying a new and highly sensitive assay for measuring N-hydroxy metabolites, the biochemical properties of the microsomal N-hydroxylase from control and 3-methylcholanthrene-treated rat and hamster liver have been analyzed, and the following conclusions have been drawn. (a) Due to a difference in enzyme affinity, the metabolic activation of acetylaminofluorene is more pronounced than that of aminofluorene, a fact which correlates with the difference in the carcinogenic potency of the two compounds. (b) Arylamine N-hydroxylase differs qualitatively as well as quantitatively from arylamide N- hydroxylase mainly in terms of sensitivity to various in vitro inhibitors. (c) 7,8-Benzoflavone and 3-methylcholanthrene are strong inhibitors of liver microsomal N-hydroxylases. This effect could partly explain the inhibition of the hepatic tumorigenicity of acetylaminofluorene in animals simultaneously fed 3-methylcholanthrene. (d) The metabolism of acetylaminofluorene proceeds via both ring- (C-1, C-3, C-5, or C-7) and N-hydroxylation. There is clear reciprocal interaction between these various microsomal pathways. (e) The apparent increase in Km following pretreatment of the rat with 3-methylcholanthrene is due to competitive inhibition of the N-hydroxylase by some of the C-hydroxy metabolites. This effect is not seen in hamster liver.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
2-Acetilaminofluoreno
/
Microssomos Hepáticos
/
Hidrocarboneto de Aril Hidroxilases
Limite:
Animals
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
1980
Tipo de documento:
Article