Relationship of phenol sulfotransferase activity (SULT1A1) genotype to sulfotransferase phenotype in platelet cytosol.
Sulfation catalysed by human cytosolic sulfotransferases is generally considered to be a detoxification mechanism. Recently, it has been demonstrated that sulfation of heterocyclic aromatic amines by human phenol sulfotransferase (SULT1A1) can result in a DNA binding species. Therefore, sulfation capacity has the potential to influence chemical carcinogenesis in humans. To date, one genetic polymorphism (Arg213His) has been identified that is associated with reduced platelet sulfotransferase activity. In this study, data on age, race, gender, SULT1A1 genotype and platelet SULT1A1 activity were available for 279 individuals. A simple colorimetric phenotyping assay, in conjunction with genotyping, was employed to demonstrate a significant correlation (r = 0.23, P < 0.01) of SULT1A1 genotype and platelet sulfotransferase activity towards 2-naphthol, a marker substrate for this enzyme. There 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 catalysed N-hydroxy-aminobiphenyl (N-OH-ABP) DNA adduct formation with substantially 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 bound/mg DNA/20 min).
Nowell
S
S
University of Arkansas for Medical Sciences, Surgical Oncology Department, Little Rock 72205, USA. nowellsusana@exchange.uams.edu
Ambrosone
C B
CB
Ozawa
S
S
MacLeod
S L
SL
Mrackova
G
G
Williams
S
S
Plaxco
J
J
Kadlubar
F F
FF
Lang
N P
NP
D000367:Age Factors; D015239:Arylsulfotransferase; D001792:Blood Platelets / Q000201:enzymology*; D003600:Cytosol / Q000201:enzymology*; D018736:DNA Adducts / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D010641:Phenotype; D044469:Racial Groups; D012737:Sex Factors; D015238:Sulfotransferases / Q000235:genetics*
D018736:DNA Adducts; D015238:Sulfotransferases; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human