Faculty Research 1980 - 1989

Association of arylhydroxamic acid N,O-acyltransferase and genetically polymorphic N-acetyltransferase in established inbred rabbit strains.

Document Type

Article

Publication Date

1982

Keywords

Acyltransferases: ge, Alleles, Animal, Isoniazid: me, Liver: en, Male, Polymorphism-(Genetics), Rabbits: ge, SUPPORT-U-S-GOVT-P-H-S

First Page

405

Last Page

412

JAX Source

IARC-Sci-Publ. 1982; (39):405-12.

Grant

GM27028, RR00251, CA23386

Abstract

Partially purified liver preparations from 17 inbred and partially inbred rabbit strains were assayed for polymorphic N-acetyltransferase (NAT) and arylhydroxamic acid N,O-acyltransferase (AHAT) activities. The AC/J, AX/J, B/J, WH/J, X/J, Y-l/J, III/J, IIIC/J, III/DwJ, IIIEP/J and IIIVO/J inbred strains were identified as rapid acetylators and had high AHAT activity. The ACEP/J, AXBU/J, OS/J, III/cdJ, IIIVO/ahJ and IIIVO/vptJ strains were identified as slow acetylators and had low AHAT activity. These findings provide added evidence for the hypothesis that polymorphic NAT and AHAT activities are properties of the same enzyme. Additional studies in five of the rapid acetylator strains showed that they had significantly higher levels of liver NAT activity towards other arylamine acetylator predictor drugs and carcinogens than did obligate heterozygous (Rr) rapid acetylators from our rabbit colony. This indicates that the inbred animals are homozygous (RR) rapid acetylators and that there is a gene-dose response difference between the two rapid acetylator genotypes. Availability of established inbred and partially inbred strains shown to possess both acetylator phenotypes enhances the opportunity for using the rabbit as a genetic model for evaluating the role of the isoniazid acetylator polymorphism as a host factor in arylamine-related carcinogenesis.

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