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

Abstract

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).

Biological Monitoring of Bisphenol A in a Korean Population

“…Therefore, people with the rapid sulfonylation alleles would be less susceptible to BPA toxicity and would have higher levels of conjugated BPA in urine. As the SULT1A1*1 allele is known to be rapid sulfonylation allele (Raftogianis et al 1997;Nowell et al 2000), its presence is suspected to assist rapid disposal of environmental BPA sources. However, urinary BPA levels were not significantly different between SULT1A1*1/*1 subjects and SULT1A1*1/*2 subjects in our study (Table 4).…”

“…Among phase II enzymes, sulfotransferases (SULTs) and uridine diphosphate glucuronosyltransferases (UGTs) are known to be involved in BPA metabolism (Elsby et al 2001;Yokota et al 1999;Suiko et al 2000;Raftogianis et al 1997). Among SULTs, SULT1A1 is thought to sulfate phenolic compounds like BPA, and is considered to be genetically polymorphic (Raftogianis et al 1997;Nowell et al 2000;Carlini et al 2001) in human. There are four known different alleles in SULT1A1, and are reported as: SULT1A1*1, SULT1A1*2, SULT1A1*3, and SULT1A1*4 in the literature.…”

“…Toxicol. 44, 546 -551 (2003) DOI: 10.1007/s00244-002-2124 A R C H I V E S O F Environmental Contamination a n d Toxicology transition results in an Arg 213 to His alteration in the amino acid sequence and leads to lower enzyme activity in people with SULT1A1*2 than in people with SULT1A1*1 (Raftogianis et al 1997;Nowell et al 2000;Carlini et al 2001). Thus, urinary BPA levels can be affected by the genetic polymorphism of SULT1A1.…”

Pharmacogenetics of human cytosolic sulfotransferases

“…This coordinate regulation of enzyme activity and the accessibility of platelets led to their use as a surrogate for enzyme activity in human population studies. Some studies have shown that SULT1A1 platelet enzymatic activity varies by gender and by season (Marazziti et al, 1995(Marazziti et al, , 1998Nowell et al, 2000). Interestingly, megakaryocytes, parental cells of the platelet, express both estrogen and androgen receptors, leading to the speculation that steroids could modulate the expression of enzymes found in the platelet (Tarantino et al, 1994;Khetawat et al, 2000).…”

“…A study by Brittelli et al (1999) showed that SULT1A1 activity was significantly different between Spaniards and Finns, and in the case of the Finnish population, phenotype also varied by gender. Platelet SULT1A1 phenotype also tends to be higher in African Americans compared to Caucasians (Anderson et al, 1988;Nowell et al, 2000).…”