Environmental, dietary, maternal, and fetal predictors of bulky DNA adducts in cord blood: a European mother-child study (NewGeneris)

Abstract

B ackground : Bulky DNA adducts reflect genotoxic exposures, have been associated with lower birth weight, and may predict cancer risk. o Bjective : We selected factors known or hypothesized to affect in utero adduct formation and repair and examined their associations with adduct levels in neonates. M ethods : Pregnant women from Greece, Spain, England, Denmark, and Norway were recruited in 2006–2010. Cord blood bulky DNA adduct levels were measured by the 32 P-postlabeling technique ( n = 511). Diet and maternal characteristics were assessed via questionnaires. Modeled exposures to air pollutants and drinking-water disinfection by-products, mainly trihalomethanes (THMs), were available for a large proportion of the study population. r esults : Greek and Spanish neonates had higher adduct levels than the northern European neonates [median, 12.1 ( n = 179) vs. 6.8 ( n = 332) adducts per 108 nucleotides, p < 0.001]. Residence in southern European countries, higher maternal body mass index, delivery by cesarean section, male infant sex, low maternal intake of fruits rich in vitamin C, high intake of dairy products, and low adherence to healthy diet score were statistically significantly associated with higher adduct levels in adjusted models. Exposure to fine particulate matter and nitrogen dioxide was associated with significantly higher adducts in the Danish subsample only. Overall, the pooled results for THMs in water show no evidence of association with adduct levels; however, there are country-specific differences in results with a suggestion of an association in England. c onclusion : These findings suggest that a combination of factors, including unknown country- specific factors, influence the bulky DNA adduct levels in neonates. c itation : Pedersen M, Mendez MA, Schoket B, Godschalk RW, Espinosa A, Landström A, Villanueva CM, Merlo DF, Fthenou E, Gracia-Lavedan E, van Schooten FJ, Hoek G, Brunborg G, Meltzer HM, Alexander J, Nielsen JK, Sunyer J, Wright J, Kovács K, de Hoogh K, Gutzkow KB, Hardie LJ, Chatzi L, Knudsen LE, Anna L, Ketzel M, Haugen M, Botsivali M, Nieuwenhuijsen MJ, Cirach M, Toledano MB, Smith RB, Fleming S, Agramunt S, Kyrtopoulos SA, Lukács V, Kleinjans JC, Segerbäck D, Kogevinas M. 2015. Environmental, dietary, maternal, and fetal predic- tors of bulky DNA adducts in cord blood: a European mother–child study