Marco Sánchez-Guerraa, E-mail The Corresponding Author, Nadia Pelallo-Martínezb, E-mail The Corresponding Author, Fernando Díaz-Barrigab, E-mail The Corresponding Author, Stephen J. Rothenberga, c, E-mail The Corresponding Author, Leticia Hernández-Cadenac, E-mail The Corresponding Author, Sylvain Faugerond, E-mail The Corresponding Author, Luis F. Oropeza-Hernándeze, E-mail The Corresponding Author, Margarita Guaderrama-Díaza, E-mail The Corresponding Author, Betzabet Quintanilla-Vegaa, Corresponding Author Contact Information
http://www.sciencedirect.com/science/ar ... 1811003597
Received 22 September 2011; revised 2 December 2011; Accepted 8 December 2011. Available online 17 December 2011.
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants presenting a public health risk, particularly to children, a vulnerable population. PAHs have genotoxic and carcinogenic properties, which depend on their metabolism. Many enzymes involved in PAH metabolism, including CYP1A1, CYP1B1, GSTM and GSTT are polymorphic, which may modulate the activation/deactivation of these compounds. We evaluated PAH exposure and DNA damage in children living in the vicinity of the main petrochemical complex located in the Gulf of Mexico, and explored the modulation by genetic polymorphisms of PAH excretion and related DNA damage. The participants (n = 82) were children aged 6–10 y attending schools near the industrial area. Urinary 1-hydroxypyrene (1-OHP; a biomarker of PAH exposure) was determined by reverse-phase-HPLC; DNA damage by the comet assay (Olive Tail Moment (OTM) parameter); CYP1A1*2C and CYP1B1*3 polymorphisms by real time-PCR; and GSTM1*0 and GSTT1*0 by multiplex PCR. The median value of 1-OHP was 0.37 μmol/mol creatinine; 59% of children had higher 1-OHP concentrations than those reported in environmentally exposed adults (0.24 μmol/mol creatinine). A stratified analysis showed increased DNA damage in children with 1-OHP concentrations greater than the median value. We observed higher 1-OHP concentrations in children with CYP1A1*2C or GSTM1*0 polymorphisms, and a positive influence of CYP1A1*2C on OTM values in children with the highest PAH exposure. The data indicate that children living in the surroundings of petrochemical industrial areas are exposed to high PAH levels, contributing to DNA damage and suggesting an increased health risk; furthermore, data suggest that polymorphisms affecting activation enzymes may modulate PAH metabolism and toxicity.
► Children from the studied industrial site are exposed to high PAH level. ► Environmental high PAH exposure is related to DNA damage in children. ► Environmental PAH exposure limit has to be established. ► Alteration on 1-OHP excretion by genetic polymorphisms may also modify PAH toxicity.
Abbreviations: CYP, cytochrome P450; GST, glutathione-S-transferase; 1-OHP, 1-hydroxypyrene; PAH, polycyclic aromatic hydrocarbon; UGT, UDP-glucuronosyl transferase
Keywords: PAH metabolism; 1-Hydroxypyrene; DNA damage; Environmental exposures; Genetic polymorphisms
2. Materials and methods
2.1. Study population
2.2. Sample collection and analysis
2.3. DNA extraction and genotyping
2.4. Comet assay
2.5. Statistical analyses
3.1. Children's characteristics and their influence on urinary 1-OHP concentrations
3.2. DNA damage
3.3. Genetic polymorphisms
3.4. Influence of genetic polymorphisms of PAH metabolizing enzymes on the biomarker of exposure (1-OHP)
3.5. Influence of genetic polymorphisms of PAH metabolizing enzymes on DNA damage
Conflict of interest statement
Corresponding Author Contact InformationCorresponding author at: Ave. IPN 2508, Col. Zacatenco, Mexico City 07360, Mexico. Tel.: +52 55 57473800x5446; fax: +52 55 57473395.