Relationship of phenol sulfotransferase activity (SULT1A1) genotype to sulfotransferase phenotype in platelet cytosol

Sulfation catalysed by human cytosolic sulfotransferases is generally consi dered to be a detoxification mechanism, Recently, it has been demonstrated that sulfation of heterocyclic aromatic amines by human phenol sulfotransfe rase (SULT1A1) can result in a DNA binding species. Therefore, sulfation ca pacity has the potential to influence chemical carcinogenesis in humans, To date, one genetic polymorphism (Arg(213)His) has been identified that is a ssociated with reduced platelet sulfotransferase activity. In this study, d ata on age, race, gender, SULT1A1 genotype and platelet SULT1A1 activity we re available for 279 individuals. A simple colorimetric phenotyping assay, in conjunction with genotyping, was employed to demonstrate a significant c orrelation (r = 0.23, P < 0.01) of SULT1A1 genotype and platelet sulfotrans ferase activity towards 2-naphthol, a marker substrate for this enzyme. The re was also a difference in mean sulfotransferase activity based on gender (1.28 nmol/min/mg, females; 0.94 nmol/min/mg, males, P=0.001). DNA binding studies using recombinant SULT1A1*1 and SULT1A1*2 revealed that SULT1A1*1 c atalysed N-hydroxy-aminobiphenyl (N-OH-ABP) DNA adduct formation with subst antially greater efficiency (5.4 versus 0.4 pmol bound/mg DNA/20 min) than the SULT1A1*2 variant. A similar pattern was observed with 2-hydroxyamino-1 -methyl-6-phenylimidazo[4,5b]pyridine (N-OH-PhIP) (4.6 versus 1.8 pmol boun d/mg DNA/20 min). Pharmacogenetics 10:789-797 (C) 2000 Lippincott Williams & Wilkins.