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Carcinogenesis Advance Access published online on March 23, 2009
Carcinogenesis, doi:10.1093/carcin/bgp062
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© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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

Antonio Agudo1, Marco Peluso2, Núria Sala1,3, Gabriel Capellá3, Armelle Munnia2, Sara Piro2, Fátima Marín3, Raquel Ibáñez1, Pilar Amiano4,5, M. José Tormo5,6, Eva Ardanaz5,7, Aurelio Barricarte5,7, M. Dolores Chirlaque5,6, Miren Dorronsoro4,5, Nerea Larrañaga4,5, Carmen Martínez5,8, Carmen Navarro5,6, J. Ramón Quirós9, M. José Sánchez5,8 and Carlos A. González1

1 Unit of Nutrition, Environment, and Cancer. Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), IDIBELL. L'Hospitalet de Llobregat, 08907 Spain
2 Cancer Risk Factor Branch, Molecular Biology Laboratory, CSPO-Scientific Institute of Tuscany Region, Florence, Italy
3 Translational Research Laboratory, Catalan Institute of Oncology (ICO), IDIBELL. L'Hospitalet de Llobregat, 08907 Spain
4 Dirección de Salud de Guipúzcoa, 20013 San Sebastian, Spain
5 CIBER Epidemiología y Salud Pública (CIBERESP), Spain
6 Consejería de Sanidad y Consumo, 3008 Murcia, Spain
7 Instituto de Salud Pública de Navarra, 31003 Pamplona, Spain
8 Escuela Andaluza de Salud Pública, 18080 Granada, Spain
9 Consejería de Sanidad y Servicios Sociales de Asturias, 33001 Oviedo, Spain

Address correspondence to Antonio Agudo, MD, MSc, PhD. Unit of Nutrition, Environment, and Cancer. Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO). Av. Gran Via s/n km 2.7, 08907 L'Hospitalet de Llobregat, Spain. Phone +34 932607401. Fax +34 932607787. E-mail: a.agudo{at}iconcologia.net.

Aromatic compounds such as polycyclic aromatic hydrocarbons (PAH), arylamines (AA), and heterocyclic amines (HA), 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 (WBC) by the 32P-Postlabelling assay in a sample of 296 healthy adults (147 men and 149 women) from five regions of Spain. We also analysed functional polymorphisms in the metabolic genes CYP1A1, CYP1A2, EPHX1, GSTM, 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 1.56x10-9adducts, 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-labelling assay a firm conclusion cannot be drawn.

Received December 28, 2007; revised May 27, 2008; accepted May 29, 2008.


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