title: Environmental polycyclic aromatic hydrocarbon (PAH) exposure and DNA damage in Mexican children.
abstract: 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 6-10y 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 0.37μmol/mol creatinine; 59% of children had higher 1-OHP concentrations than those reported in environmentally exposed adults (0.24μmol/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.
authors.affiliation: Departamento de Toxicología, CINVESTAV-IPN, Mexico, Mexico. masanchez@cinvestav.mx
authors.forename: Marco
authors.initials: M
authors.lastname: Sánchez-Guerra
authors.forename: Nadia
authors.initials: N
authors.lastname: Pelallo-Martínez
authors.forename: Fernando
authors.initials: F
authors.lastname: Díaz-Barriga
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Rothenberg
authors.forename: Leticia
authors.initials: L
authors.lastname: Hernández-Cadena
authors.forename: Sylvain
authors.initials: S
authors.lastname: Faugeron
authors.forename: Luis F
authors.initials: LF
authors.lastname: Oropeza-Hernández
authors.forename: Margarita
authors.initials: M
authors.lastname: Guaderrama-Díaz
authors.forename: Betzabet
authors.initials: B
authors.lastname: Quintanilla-Vega
mesh_terms: D002648:Child; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D004249:DNA Damage / Q000187:drug effects*; D004781:Environmental Exposure; D005260:Female; D006801:Humans; D008297:Male; D008800:Mexico; D011084:Polycyclic Aromatic Hydrocarbons / Q000378:metabolism / Q000633:toxicity*; D011110:Polymorphism, Genetic; D011721:Pyrenes / Q000493:pharmacokinetics
chemical_list: D011084:Polycyclic Aromatic Hydrocarbons; D011721:Pyrenes; C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1; C033146:1-hydroxypyrene