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Relationships between Dapsone Metabolic Activity and Polymorphism of Arylamine N-acetyltransferase 2 in the F2 Hybrid Rats  

신인철 (한양대학교 의과대학 약리학교실 및 의과학연구소)
강주섭 (한양대학교 의과대학 약리학교실 및 의과학연구소)
고현철 (한양대학교 의과대학 약리학교실 및 의과학연구소)
이창호 (한양대학교 의과대학 약리학교실 및 의과학연구소)
안동춘 (강원대학교 동물지원과학대학 수의학과)
백두진 (한양대학교 의과대학 해부학교실)
심성한 (한양대학교 의과대학 유전학교실)
조율희 (한양대학교 의과대학 유전학교실)
Publication Information
Biomolecules & Therapeutics / v.10, no.3, 2002 , pp. 193-199 More about this Journal
The arylamine N-acetyltransferases (NATs) are a family of enzymes that N-acetylate mylhydrazines and arylamines through transfer of an acetyl group from acetyl coenzyme A. This activity was found to vary among individuals as a Mendalian trait and the basis of the genetic differences in human NAT activity is one of the best of the genetic studied examples of pharmacogenetic variation. The classical N-acetylation polymorphism is regulated at the NAT2 locus, which segregates individuals into rapid, intermediate, and slow acetylator phenotypes. In this study, the relationship between NAT2 activity phenotype using HPLC:UV assay for the determination of dapsone and monoacetyldapsone in plasma and NAT2 genotype by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) was investigated in the F2 hybrid (Fischer 344 vs Wistar-Kyoto) rats. Three Common mutant alleles at the NAT2 gene locus have been identified in the F2 generation progeny of Fischer 344 rats as raid acetylator and Wistar-Kyoto rats as slow acetylator segregated into three modes (low, intermediates, and high) with simple Mendelian inheritance. The metabolic activity of NAT2 of the intermediate and rapid acetylators is significant1y greater than slow acetylator, but the metabolic activity of rapid acetylator is not significantly different from Intermediate type. Therefore, we could observe that complete trimodal NAT2 genotypic alleles and incomplete trimodal NAT2 metabolic phenotypic distribution in tile F2 hybrid rats. These observations suggest that the relationships between NAT2 genotype and metabolic phenotype exists and F2 hybrid (Fischer 344: Wistar-Kyoto) animal models about NAT2 polymorphism might be applied in the toxicity and pharmacogenetic studies of arylamine drugs and carcinogens.
Fischer 344 rat; Wistar-Kyoto rat; F2 hybrids; N-acetyltransferase(NAT); arylamine; dapsone; monoacetyldapsone; acetylators;
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