Document Detail

Detoxication of benzo[a]pyrene-7,8-dione by sulfotransferases (SULTs) in human lung cells.
MedLine Citation:
PMID:  22782890     Owner:  NLM     Status:  MEDLINE    
Polycyclic aromatic hydrocarbons (PAH) are environmental and tobacco carcinogens. Human aldo-keto reductases catalyze the metabolic activation of proximate carcinogenic PAH trans-dihydrodiols to yield electrophilic and redox-active o-quinones. Benzo[a]pyrene-7,8-dione a representative PAH o-quinone is reduced back to the corresponding catechol to generate a futile redox-cycle. We investigated whether sulfonation of PAH catechols by human sulfotransferases (SULT) could intercept the catechol in human lung cells. RT-PCR identified SULT1A1, -1A3, and -1E1 as the isozymes expressed in four human lung cell lines. The corresponding recombinant SULTs were examined for their substrate specificity. Benzo[a]pyrene-7,8-dione was reduced to benzo[a]pyrene-7,8-catechol by dithiothreitol under anaerobic conditions and then further sulfonated by the SULTs in the presence of 3'-[(35)S]phosphoadenosine 5'-phosphosulfate as the sulfonate group donor. The human SULTs catalyzed the sulfonation of benzo[a]pyrene-7,8-catechol and generated two isomeric benzo[a]pyrene-7,8-catechol O-monosulfate products that were identified by reversed phase HPLC and by LC-MS/MS. The various SULT isoforms produced the two isomers in different proportions. Two-dimensional (1)H and (13)C NMR assigned the two regioisomers of benzo[a]pyrene-7,8-catechol monosulfate as 8-hydroxy-benzo[a]pyrene-7-O-sulfate (M1) and 7-hydroxy-benzo[a]pyrene-8-O-sulfate (M2), respectively. The kinetic profiles of three SULTs were different. SULT1A1 gave the highest catalytic efficiency (k(cat)/K(m)) and yielded a single isomeric product corresponding to M1. By contrast, SULT1E1 showed distinct substrate inhibition and formed both M1 and M2. Based on expression levels, catalytic efficiency, and the fact that the lung cells only produce M1, it is concluded that the major isoform that can intercept benzo[a]pyrene-7,8-catechol is SULT1A1.
Li Zhang; Meng Huang; Ian A Blair; Trevor M Penning
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-07-09
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-27     Completed Date:  2012-11-19     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  29909-20     Citation Subset:  IM    
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MeSH Terms
Arylsulfotransferase / genetics,  metabolism*
Benzopyrenes / pharmacokinetics*,  pharmacology
Cell Line, Tumor
Gene Expression Regulation, Enzymologic / drug effects*,  genetics
Gene Expression Regulation, Neoplastic / drug effects*,  genetics
Isoenzymes / genetics,  metabolism
Lung Neoplasms / enzymology*,  genetics,  pathology
Neoplasm Proteins / biosynthesis*,  genetics
Grant Support
P30 CA016520/CA/NCI NIH HHS; P30 ES013508/ES/NIEHS NIH HHS; P30-ES-013508/ES/NIEHS NIH HHS; PA-DOH4100038714//PHS HHS; R01 CA039504/CA/NCI NIH HHS; R01-CA39504/CA/NCI NIH HHS
Reg. No./Substance:
0/Benzopyrenes; 0/Isoenzymes; 0/Neoplasm Proteins; 65199-11-3/benzo(a)pyrene-7,8-dione; EC

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