Aromatic DNA adducts and polymorphisms in metabolic genes in healthy adults: findings from the EPIC-Spain cohort.

2.50
Hdl Handle:
http://hdl.handle.net/10146/113569
Title:
Aromatic DNA adducts and polymorphisms in metabolic genes in healthy adults: findings from the EPIC-Spain cohort.
Authors:
Agudo, Antonio; Peluso, Marco; Sala, Nuria; Capella, Gabriel; Munnia, Armelle; Piro, Sara; Marin, Fatima; Ibanez, Raquel; Amiano, Pilar; Tormo, M. Jose; Ardanaz, Eva; Barricarte, Aurelio; Chirlaque, M. Dolores; Dorronsoro, Miren; Larranaga, Nerea; Martinez, Carmen; Navarro, Carmen; Quiros, J. Ramon; Sanchez, M. Jose; Gonzalez, Carlos A.
Abstract:
Aromatic compounds such as polycyclic aromatic hydrocarbons, arylamines and heterocyclic amines require metabolic activation to form metabolites able to bind to DNA, a process mediated by polymorphic enzymes. We measured aromatic DNA adducts in white blood cells by the (32)P-post-labelling assay in a sample of 296 healthy adults (147 men and 149 women) from five regions of Spain. We also analyzed functional polymorphisms in the metabolic genes CYP1A1, CYP1A2, EPHX1, GSTM1, GSTT1, NAT2 and SULT1A1. A significant increased level of DNA aromatic adducts was found related to the fast oxidation-hydrolysis phenotype defined by the polymorphism I462V in CYP1A1, the allele A in IVS1-154C>A of CYP1A2 and the combination Tyrosine-Arginine for Y113H and H139R of EPHX1. Geometric means (adducts per 10(-9) normal nucleotides) were 2.17, 4.04 and 6.30 for slow, normal and fast phenotypes, respectively (P-trend = 0.01). Slow acetylation by NAT2 was associated with a significant decrease in adduct level; subjects with slow alleles *5A and *7A/B had in average 1.56 x 10(-9)adducts, as compared with 5.60 for those with normal NAT2 activity (P-value = 0.01). No association was seen with polymorphisms of other metabolic genes such as GSTM1, GSTT1 or SULT1A1. We concluded that the metabolic pathways of oxidation, hydrolysis and acetylation are relevant to the formation of bulky DNA adducts. This could suggest a potential involvement of aromatic compounds in the formation of such adducts; however, given lack of specificity of the post-labeling assay, a firm conclusion cannot be drawn.
Citation:
Carcinogenesis 2009, 30 (6):968-976
Journal:
Carcinogenesis
Issue Date:
Jun-2009
URI:
http://hdl.handle.net/10146/113569
DOI:
10.1093/carcin/bgp062
PubMed ID:
19307236
Additional Links:
http://carcin.oxfordjournals.org/content/30/6/968.long
Type:
Article
Language:
en
ISSN:
1460-2180
Sponsors:
European Commission (SO 97 200302 05F02); Spanish Ministry of Health (Exp. 02-0652); Red Tema´tica de Investigacio´n Cooperativa de Centros de Ca´ncer (C03/10); Regional Governments; International Agency for Research on Cancer (AEP/93/02); Institut d’Investigacio´ Biome`dica de Bellvitge (R.I.); Environmental Cancer Risk, Nutrition and Individual Susceptibility, a Network of Excellence of the 6th EU Framework Program (FP6, FOOD-CT-2005-513 943 to A.A., C.A.G., N.S., G.C.).
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorAgudo, Antonioen
dc.contributor.authorPeluso, Marcoen
dc.contributor.authorSala, Nuriaen
dc.contributor.authorCapella, Gabrielen
dc.contributor.authorMunnia, Armelleen
dc.contributor.authorPiro, Saraen
dc.contributor.authorMarin, Fatimaen
dc.contributor.authorIbanez, Raquelen
dc.contributor.authorAmiano, Pilaren
dc.contributor.authorTormo, M. Joseen
dc.contributor.authorArdanaz, Evaen
dc.contributor.authorBarricarte, Aurelioen
dc.contributor.authorChirlaque, M. Doloresen
dc.contributor.authorDorronsoro, Mirenen
dc.contributor.authorLarranaga, Nereaen
dc.contributor.authorMartinez, Carmenen
dc.contributor.authorNavarro, Carmenen
dc.contributor.authorQuiros, J. Ramonen
dc.contributor.authorSanchez, M. Joseen
dc.contributor.authorGonzalez, Carlos A.en
dc.date.accessioned2010-10-20T13:17:01Z-
dc.date.available2010-10-20T13:17:01Z-
dc.date.issued2009-06-
dc.identifier.citationCarcinogenesis 2009, 30 (6):968-976en
dc.identifier.issn1460-2180-
dc.identifier.pmid19307236-
dc.identifier.doi10.1093/carcin/bgp062-
dc.identifier.urihttp://hdl.handle.net/10146/113569-
dc.description.abstractAromatic compounds such as polycyclic aromatic hydrocarbons, arylamines and heterocyclic amines require metabolic activation to form metabolites able to bind to DNA, a process mediated by polymorphic enzymes. We measured aromatic DNA adducts in white blood cells by the (32)P-post-labelling assay in a sample of 296 healthy adults (147 men and 149 women) from five regions of Spain. We also analyzed functional polymorphisms in the metabolic genes CYP1A1, CYP1A2, EPHX1, GSTM1, GSTT1, NAT2 and SULT1A1. A significant increased level of DNA aromatic adducts was found related to the fast oxidation-hydrolysis phenotype defined by the polymorphism I462V in CYP1A1, the allele A in IVS1-154C>A of CYP1A2 and the combination Tyrosine-Arginine for Y113H and H139R of EPHX1. Geometric means (adducts per 10(-9) normal nucleotides) were 2.17, 4.04 and 6.30 for slow, normal and fast phenotypes, respectively (P-trend = 0.01). Slow acetylation by NAT2 was associated with a significant decrease in adduct level; subjects with slow alleles *5A and *7A/B had in average 1.56 x 10(-9)adducts, as compared with 5.60 for those with normal NAT2 activity (P-value = 0.01). No association was seen with polymorphisms of other metabolic genes such as GSTM1, GSTT1 or SULT1A1. We concluded that the metabolic pathways of oxidation, hydrolysis and acetylation are relevant to the formation of bulky DNA adducts. This could suggest a potential involvement of aromatic compounds in the formation of such adducts; however, given lack of specificity of the post-labeling assay, a firm conclusion cannot be drawn.en
dc.description.sponsorshipEuropean Commission (SO 97 200302 05F02); Spanish Ministry of Health (Exp. 02-0652); Red Tema´tica de Investigacio´n Cooperativa de Centros de Ca´ncer (C03/10); Regional Governments; International Agency for Research on Cancer (AEP/93/02); Institut d’Investigacio´ Biome`dica de Bellvitge (R.I.); Environmental Cancer Risk, Nutrition and Individual Susceptibility, a Network of Excellence of the 6th EU Framework Program (FP6, FOOD-CT-2005-513 943 to A.A., C.A.G., N.S., G.C.).en
dc.language.isoenen
dc.relation.urlhttp://carcin.oxfordjournals.org/content/30/6/968.longen
dc.subjectPolycyclic Hydrocarbonsen
dc.subjectDNA Adductsen
dc.subjectAryl Hydrocarbon Hydroxylasesen
dc.subjectArylamine N-Acetyltransferaseen
dc.subjectArylsulfotransferaseen
dc.subjectEpoxide Hydrolasesen
dc.subjectGlutathione Transferaseen
dc.subjectHumansen
dc.subjectPolymorphismen
dc.subjectOxidation-Reductionen
dc.subjectAcetylationen
dc.subjectCohort Studiesen
dc.subject.meshAcetylation-
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAryl Hydrocarbon Hydroxylases-
dc.subject.meshArylamine N-Acetyltransferase-
dc.subject.meshArylsulfotransferase-
dc.subject.meshCohort Studies-
dc.subject.meshDNA Adducts-
dc.subject.meshEpoxide Hydrolases-
dc.subject.meshFemale-
dc.subject.meshGlutathione Transferase-
dc.subject.meshHumans-
dc.subject.meshHydrolysis-
dc.subject.meshLeukocytes-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshOxidation-Reduction-
dc.subject.meshPolycyclic Hydrocarbons, Aromatic-
dc.subject.meshPolymorphism, Genetic-
dc.titleAromatic DNA adducts and polymorphisms in metabolic genes in healthy adults: findings from the EPIC-Spain cohort.en
dc.typeArticleen
dc.identifier.journalCarcinogenesisen

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