Induction, activation, and inhibition of hamster and rat liver microsomal arylamide and arylamine N-hydroxylase.
(1980) Cancer research — Vol. 40, n° 10, p. 3540-3546 (1980)
Files
No attached file found for this publication.
Details
- Authors
- 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.
- Affiliations
Citations
Razzouk, C., Mercier, M., & Roberfroid, M. (1980). Induction, activation, and inhibition of hamster and rat liver microsomal arylamide and arylamine N-hydroxylase. Cancer research, 40(10), 3540-3546. https://hdl.handle.net/2078.5/135352 (Original work published 1980)