Genetic differences in the enzymic properties of the aromatic hydrocarbon inducible N-hydroxylation of 2-acetylaminofluorene in mouse liver.
(1982) Carcinogenesis : integrative cancer research — Vol. 3, n° 11, p. 1325-1329 (1982)
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- Abstract
- 3-Methylcholanthrene (3-MC) pretreatment induces the liver microsomal 2-acetylaminofluorene (2-AAF) N-hydroxylase activity of C57BL6 responsive mice. The same pretreatment modifies this enzyme by significantly increasing its apparent Km value which, moreover, becomes protein concentration dependent. After 3-MC induction, the C57BL6 mouse liver microsomal 2-AAF N-hydroxylase is activated by paraoxon and 8-hydroxyquinoline. This last chemical does not, however, inhibit the microsomal metabolism of N-hydroxy-2-acetylaminofluorene (N-OH-2-AAF) as it does in the presence of guinea pig liver microsomes. The hypothesis is formulated that 3-MC pretreatment of C57BL6 mice induces not only cytochrome P448 dependent mixed function oxidase but also the synthesis of a microsomal protein which reversibly binds 2-AAF. Mutagenicity data are presented which corroborate this hypothesis. As in guinea pig liver microsomes, N-OH-2-AAF is further metabolized by both C57BL6 and DBA2 mouse liver microsomes. This metabolism is not inhibited by NaF which acts as an inhibitor of microsomal arylamidase. This is a possible contributing reason why 2-AAF is only weakly carcinogenic for mice.
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Razzouk, C., Batardy-Grégoire, M., & Roberfroid, M. (1982). Genetic differences in the enzymic properties of the aromatic hydrocarbon inducible N-hydroxylation of 2-acetylaminofluorene in mouse liver. Carcinogenesis : integrative cancer research, 3(11), 1325-1329. https://hdl.handle.net/2078.5/85085 (Original work published 1982)