Genetic differences in the enzymic properties of the aromatic hydrocarbon inducible N-hydroxylation of 2-acetylaminofluorene in mouse liver.

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.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Razzouk C,Batardy-Grégoire M,Roberfroid M

doi

10.1093/carcin/3.11.1325

subject

Has Abstract

pub_date

1982-01-01 00:00:00

pages

1325-9

issue

11

eissn

0143-3334

issn

1460-2180

journal_volume

3

pub_type

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