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dc.contributor.authorAl-Buheissi, SZen_US
dc.contributor.authorPatel, HRen_US
dc.contributor.authorMeinl, Wen_US
dc.contributor.authorHewer, Aen_US
dc.contributor.authorBryan, RLen_US
dc.contributor.authorGlatt, Hen_US
dc.contributor.authorMiller, RAen_US
dc.contributor.authorPhillips, DHen_US
dc.identifier.citationPHARMACOGENETICS AND GENOMICS, 2006, 16 pp. 391 - 399en_US
dc.description.abstractBackground N-Acetyltransferases (NATs) and sulfotransferases (SULTs) are key phase 11 metabolizing enzymes that can be involved both in the detoxification and in the activation of many human promutagens and procarcinogens. Methods and results We investigated the expression of NATs and SULTs in human prostate and tested their role in the activation the N-hydroxy (N-OH) metabolite of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), a dietary carcinogen, to form DNA adducts. Western blotting showed detectable levels of NAT1, SULT1A1 and SULT1A3 with marked inter-individual variation. NAT2 and other SULT enzymes were not detectable. NAT1 was localized by immunohistochemistry to the cytoplasm of epithelial cells. The presence of acetyl Co-enzyme A (acetyl CoA) and 3’-phosphoadenosine-5’-phosphosulfate (PAPS), NAT and SULT cofactors, respectively, significantly increased the level of DNA adducts, detected by (32)P-postlabelling analysis, in calf thymus DNA incubated with N-OH-IQ and prostate cytosolic fractions. The enhancement in the level of DNA adducts in the presence of PAPS correlated with the level of SULT1A1 protein. A single prostate cytosol with the SULT1A1 *2/*2 genotype produced less DNA adducts than cytosols with the *1/*2 and *1/*1 genotypes. No significant correlation was observed between NAT1 protein level and the formation of DNA adducts, even in the presence of acetyl CoA. Conclusions In conclusion, we demonstrated that NAT1, SULT1A1 and SULT1A3 are present in human prostate and that both enzyme classes significantly contribute to the activation of N-hydroxylated heterocyclic amines to DNA-damaging species in this tissue. Variation in expression levels, in combination with dietary and/or environmental exposure to carcinogens, could be influential in determining individual susceptibility to prostate cancer. (C) 2006 Lippincott Williams & Wilkins.en_US
dc.format.extent391 - 399en_US
dc.titleN-acetyltransferase and sulfotransferase activity in human prostate: potential for carcinogen activationen_US
dc.typeJournal Article
rioxxterms.typeJournal Article/Reviewen_US
pubs.notesaffiliation: Al-Buheissi, SZ (Reprint Author), Inst Canc Res, Sect Mol Carcinogenesis, Brookes Lawley Bldg,Cotswold Rd, Sutton SM2 5NG, Surrey, England. Inst Canc Res, Sect Mol Carcinogenesis, Sutton SM2 5NG, Surrey, England. German Inst Human Nutr, Dept Toxicol, Nuthetal, Germany. Whittington Hosp, Dept Urol, London N19 5NF, England. Whittington Hosp, Dept Histopathol, London N19 5NF, England. UCL Hosp, Inst Urol, London, England. keywords: N-acetyltransferase; sulfotransferase; phase II enzymes; carcinogen activation; human prostate keywords-plus: XENOBIOTIC-METABOLIZING ENZYMES; HETEROCYCLIC AROMATIC-AMINES; RECOMBINANT HUMAN NAT1; SALMONELLA-TYPHIMURIUM; DNA-ADDUCTS; HUMAN CYTOCHROMES-P-450; TISSUE DISTRIBUTION; EXPRESSION; GENOTYPE; BINDING research-areas: Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy web-of-science-categories: Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy author-email: orcid-numbers: Phillips, David/0000-0001-8509-3485 Glatt, Hansruedi/0000-0001-6053-0562 number-of-cited-references: 56 times-cited: 16 usage-count-last-180-days: 0 usage-count-since-2013: 2 journal-iso: Pharmacogenet. Genomics doc-delivery-number: 162ZD unique-id: ISI:000246127100002 da: 2018-09-04en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Human Biomonitoring & Carcinogen Activation
pubs.embargo.termsNot knownen_US
icr.researchteamHuman Biomonitoring & Carcinogen Activationen_US
dc.contributor.icrauthorPhillips, David Hunteren_US

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