Sulfotransferases: genetics and role in toxicology

Glatt, Hansruedi; Engelke, Christina E.H; Pabel, Ulrike; Teubner, Wera; Jones, A. L.; Coughtrie, Michael W.H.; Andrae, U.; Falany, Charles N.; Meinl, Walter

doi:10.1016/s0378-4274(99)00214-3

Cited by 126 publications

(93 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Desulfation regenerates the active form of the compound and renders it capable of exerting a biological effect. Both the SULTs and STS are widely distributed in human tissues (6,7,31) although several of the SULT isoforms demonstrate important tissue specific activity in steroid metabolism (8,13,22,33). The sulfation of Tib and its active metabolites in human endometrial cells by SULT1E1 is important for preventing the estrogenic activity of Tib in human endometrial tissues by selecting the generation of the progestagenic Δ4-isomer (13).…”

Section: Discussionmentioning

confidence: 99%

“…Conjugation of estrogens, therapeutic estrogenic compounds as well as HRT agents with a sulfonate group is important in the regulation of their activity and disposition. Sulfation is essentially an inactivation reaction, inhibiting the biological activity of steroids by preventing binding to specific hormone receptors (6)(7)(8). In humans, Tib is rapidly metabolized into its main active metabolites, 3α-OH Tib and 3β-OH Tib, as well as a Δ4-isomer (1,9).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Interactions of the human cytosolic sulfotransferases and steroid sulfatase in the metabolism of tibolone and raloxifene

Falany

2007

The Journal of Steroid Biochemistry and Molecular Biology

View full text Add to dashboard Cite

Sulfation is important in the metabolism and inactivation of steroidal compounds and hormone replacement therapeutic (HRT) agents in human tissues. Although generally inactive, many steroid sulfates are hydrolyzed to their active forms by sulfatase activity. Therefore, the specific sulfotransferase (SULT) isoforms and the levels of steroid sulfatase (STS) activity in tissues are important in regulating the activity of steroidal and HRT compounds. Tibolone (Tib) is metabolized to three active metabolites and all four compounds are readily sulfated. Tib and the Δ4-isomer are sulfated at the 17β-OH group by SULT2A1 and the 17-sulfates are resistant to hydrolysis by human placental STS. 3α-OH and 3β-OH Tib can form both 3-and 17-monosulfates as well as disulfates. Only the 3β-sulfates are susceptible to STS hydrolysis. Raloxifene monosulfation was catalyzed by at least seven SULT isoforms and SULT1E1 also synthesizes raloxifene disulfate. SULT1E1 forms both monosulfates in a ratio of approximately 8:1 with the more abundant monosulfate migrating on HPLC identical to the SULT2A1 synthesized monosulfate. The raloxifene monosulfate formed by both SULT isoforms is sensitive to STS hydrolysis whereas the low abundance monosulfate formed by SULT1E1 is resistant. The benzothiophene sulfates of raloxifene and arzoxifene were hydrolyzed by STS whereas the raloxifene 4′-phenolic sulfate was resistant. These results indicate that tissue specific expression of SULT isoforms and STS could be important in the inactivation and regeneration of the active forms of HRT agents.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Interactions of the human cytosolic sulfotransferases and steroid sulfatase in the metabolism of tibolone and raloxifene

Falany

2007

The Journal of Steroid Biochemistry and Molecular Biology

View full text Add to dashboard Cite

show abstract

“…[2][3][4]6 The precise way that SULT1A1 influences cancer development and whether certain SULT1A1 genotypes predispose to cancer are not clear at this time. 5,6,[12][13][14][15] In an in vitro study, Glatt et al 12 found that promutagens such as 2-nitropropane were more efficiently activated by the arg allele than by the his allele in the Salmonella or V79 system. One DNA binding study done by Norwell et al, 13 however, showed that the arg allele catalyzed N-hydroxy-aminobiphenyl DNA adduct formation with substantially greater efficiency (5.4 vs. 0.4 pmol bound/mg DNA/20 min) than the his allele.…”

Section: Discussionmentioning

confidence: 99%

SULT1A1 polymorphism and esophageal cancer in males

Wang

et al. 2002

Intl Journal of Cancer

View full text Add to dashboard Cite

Sulfotransferase (SULT) 1A1 detoxifies and bioactivates a broad spectrum of substrates including xenobiotics. It has been suggested that the SULT1A1 his (histidine) allele, which is caused by a his for arg (arginine) substitution due to a G3 A transition at codon 213, carries a significantly higher risk for women to develop breast cancer. We investigated the association between the SULT1A1 arg/his genotype and esophageal cancer in men, 187 cases of esophageal squamous cell carcinoma and 308 controls from 3 medical centers in Taiwan. Cigarette smoking, areca chewing and alcohol consumption were the major risks for developing esophageal cancer. The frequencies of arg/his in cases and controls were 27.8% (52/187) and 11.0% (34/308), respectively (p < 0.0001). No subjects carried his/his. After adjusting for substance use and other covariates, individuals with arg/his had a 3.53-fold higher risk (95% CI ‫؍‬ 2.12-5.87) of developing esophageal cancer than those with arg/arg. Unexpectedly, this positive association was found to be even stronger (adjusted OR ‫؍‬ 4.04 -4.80) among non-smokers, non-drinkers or non-chewers. Our findings suggest that the SULT1A1 his 213 allele is important in the development of esophageal cancer in men.

show abstract

“…Human sulfotransferases (SULTs) catalyze the conjugation of sulfate groups to a variety of endogen and exogenous substrates, including many drugs, neurotransmitters, thyroid and steroid hormones and pro-carcinogenic agents (1,2). SULTs are genetically polymorphic and are expressed in a wide variety of tissues, such as the liver, lung, brain, kidney, and platelets (3).…”

Section: Introductionmentioning

confidence: 99%