Inter-individual variation in the mutagenic activation of 2-acetylaminofluorene by human liver in relation to animal metabolic models.

Abstract:

:A relatively large, reproducible inter-individual variation was found in the ability of 17 human liver S9 samples to mediate the mutagenicity of 2-acetylaminofluorene (2AAF) in Salmonella typhimurium strain TA98. In an animal model, variation in metabolic activation of 2AAF did not appear to relate to the phenotype of debrisoquine 4-hydroxylase since hepatic S9 from poor and extensive metabolizer phenotypes (female DA and female Wistar rat, respectively) mediated the mutagenicity of this aromatic amide equally well. Approximately one-third of human liver samples exhibited an ability to detoxify 2AAF in a modified bacterial mutagenicity assay in a manner similar to that shown by guinea pig (but not rat or rabbit) S9. However, only in 2/14 human preparations was the detoxification inhibited by 8-hydroxyquinoline which has previously been recognized as an inhibitor of a detoxifying 'transoxygenation' in guinea pig liver. The results support a growing body of evidence for inter-individual variation in human carcinogen metabolism which may be important in determining susceptibility to chemical carcinogenesis.

journal_name

Mutagenesis

journal_title

Mutagenesis

authors

Smith AJ,Chipman JK

doi

10.1093/mutage/3.4.323

subject

Has Abstract

pub_date

1988-07-01 00:00:00

pages

323-8

issue

4

eissn

0267-8357

issn

1464-3804

journal_volume

3

pub_type

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