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Dietary benzo(a)pyrene and fetal growth: effect modification by vitamin C intake and glutathione S-transferase P1 polymorphism.

ABSTRACT: Previous studies have reported maternal exposure to airborne polycyclic aromatic hydrocarbons (PAH), as well as DNA adducts reflecting total PAH exposure, to be associated with reduced fetal growth. The role of diet, the main source of PAH exposure among non-smokers, remains uncertain.To assess associations between birth weight, length and small size for gestational age (SGA) with maternal intakes of the genotoxic PAH benzo(a)pyrene [B(a)P] during pregnancy, exploring potential effect modification by dietary intakes of vitamin C, vitamin E, alpha- and beta-carotene, as well as glutathione S-transferase P1 (GSTP1) polymorphisms, hypothesized to influence PAH metabolism.657 women in the INMA (Environment and Childhood) Project from Sabadell (Barcelona) were recruited during the first trimester of pregnancy. Dietary B(a)P and nutrient intakes were estimated from food consumption data. Genotyping was conducted for the Ile105Val variant of GSTP1. Multivariable models were used to assess associations between size at birth and dietary B(a)P, evaluating potential interactions with candidate nutrients and GSTP1 variants.There were significant interactions between elevated intakes of vitamin C (above the mean of 189.41 mg/day) and dietary B(a)P during the first trimester of pregnancy in models for birth weight and length (P<0.05), but no interactions were found with other nutrients. B(a)P intakes were associated with significant reductions in birth weight and length (coefficient±SE for a 1-SD increase in B(a)P: -101.63±34.62 g and -0.38±0.16 cm, respectively) among women with low, but not high, vitamin C intakes. Elevated dietary B(a)P was also associated with increased risk of SGA births among women with low dietary vitamin C. Among these women, associations were strongest in those carrying the GSTP1 Val allele, associated with lower contaminant detoxification activity.Results suggest that dietary B(a)P exposure may impair fetal growth, particularly in genetically susceptible populations, and that increasing maternal intakes of vitamin C may help to reduce any adverse effects.

SUBMITTER: Duarte-Salles T

PROVIDER: S-EPMC3855239 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Dietary benzo(a)pyrene and fetal growth: effect modification by vitamin C intake and glutathione S-transferase P1 polymorphism.

Duarte-Salles Talita T Mendez Michelle A MA Morales Eva E Bustamante Mariona M Rodríguez-Vicente Agueda A Kogevinas Manolis M Sunyer Jordi J

Environment international 20120505

<h4>Background</h4>Previous studies have reported maternal exposure to airborne polycyclic aromatic hydrocarbons (PAH), as well as DNA adducts reflecting total PAH exposure, to be associated with reduced fetal growth. The role of diet, the main source of PAH exposure among non-smokers, remains uncertain.<h4>Objective</h4>To assess associations between birth weight, length and small size for gestational age (SGA) with maternal intakes of the genotoxic PAH benzo(a)pyrene [B(a)P] during pregnancy, ...[more]

PMID: 22565211

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Project description:Glutathione S-transferase P1 is a Phase II cytoprotective and detoxifying enzyme that is widely expressed in human airways. The glutathione S-transferase P1 Ile105Val polymorphism has been linked with atopic disorders and asthma. Yet, little remains known about the regulation of allergic inflammation by glutathione S-transferase P1 in human asthmatics.To establish the effect of the glutathione S-transferase P1 Ile105Val polymorphism on allergen-induced airway inflammation and oxidant stress, and non-specific bronchial hyperresponsiveness to methacholine and reactivity to specific allergen in mild human atopic asthmatics in vivo.Five Val(105)/Val(105) , twelve Val(105)/Ile(105) and twenty Ile(105)/Ile(105) mild atopic asthmatics underwent methacholine challenge, inhaled allergen challenge and endobronchial allergen provocation through a bronchoscope. A panel of inflammatory cytokines and chemokines, F2 -isoprostanes and isofuranes, markers of oxidative stress, thromboxane B2 and immunoglobulin E were measured in bronchoalveolar lavage fluid at baseline and 24 h after allergen instillation.Asthmatics with glutathione S-transferase P1 Val(105)/Val(105) compared with asthmatics with the glutathione S-transferase P1 Val(105)/Ile(105) and Ile(105)/Ile(105) had greater generation of acute phase cytokines (TNF-?, IL-6, CXCL8), IL-12, CCL11, thromboxane B2 and immunoglobulin E at 24 h after local allergen challenge. The GSTP1 genotype had no effect on airway hyperresponsiveness to methacholine and the reactivity to specific allergen.The glutathione S-transferase P1 Ile105Val polymorphism markedly modifies allergen-provoked airway inflammation in atopic asthmatics in vivo. Modulation of the biochemical milieu in response to allergen provides a mechanistic explanation for regulatory effects of glutathione S-transferase P1 polymorphism on airway pathophysiology, and may guide improvement of future therapeutic methods in human atopic asthmatics. These findings must me confirmed in a larger study population of asthmatics with various ethnicities.

Dataset Information

Dietary benzo(a)pyrene and fetal growth: effect modification by vitamin C intake and glutathione S-transferase P1 polymorphism.

Publications

Dietary benzo(a)pyrene and fetal growth: effect modification by vitamin C intake and glutathione S-transferase P1 polymorphism.

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