Merlo D.F.
The EU project ‘Newborns and Genotoxic exposure risks’ (NewGeneris) aimed to test the hypothesis that maternal exposure to dietary compounds with carcinogenic and immunotoxic properties results in in utero exposure and molecular events in the unborn child leading to increased risk of cancer and immune disorders in later childhood. Results concerning the relationships between in utero exposure to dietary and/or environmental carcinogens and well-established and new biomarkers of exposure/early biological effect,
including 36 gene expression profile, GWAS and the in vitro cytokinesis blocked MN assay (CBMN assay) in T lymphocytic are reported. Exposure biomarkers were measured in cord blood: acrylamide (AA-) and its metabolite glycidamide (GA-), and ethylene oxide (EtO-) haemoglobin adducts, BPDE-, 32P-bulky-, M1dG- and O6- MG-DNA adducts, and the AR, DR and ERalpha CALUX levels in plasma. Some 1500 pregnant women were enrolled between 2006 and 2010 in Heraklion, Greece (Rhea cohort); Barcelona and Sabadell, Spain (IMNA cohort); Bradford, England (born in Bradford cohort); Copenhagen, Denmark (Danish biobank) and Oslo, Norway (BraMat cohort), and blood samples were collected from 1151 mother-infant dyads. following a standardised protocol. Statistical analysis was conducted according to a previously defined statistical analysis plan. Statistical modelling (multiple binomial regression) accounted for the potential confounding effect of socio-demographic, reproductive, and lifestyle factors. Exposure biomarkers showed a large variation in the European populations. No evidence of linear relationships was detected between Hb-adducts and micronucleated binucleated (MNBN) or mononucleated cells (MNMONO). A significant association was found between M1dG-DNA adduct levels and the frequency of MNBN cells although no linear exposure- effect relationship was observed. ERalpha CALUX plasma levels were significantly associated with the frequency of MNBN and MNMONO cells and AR CALUX with the frequency of MNMONO cells. Statistically significantly lower MNBN were associated with overexpression of seven genes while no association of gene expression with significant changes in the frequency of MNMONO cells was observed. Statistically significant relationships were observed between exposure biomarkers levels and gene expression. Unsupervised GWAS analyses on the interactions between exposure biomarkers and MNBN cells revealed a cluster of significant single nucleotide polymorphisms (SNPs) only for AR CALUX. SNPs from a previously selected list of biotransformation phase I and II genes were also investigated for association with MNBN cells. Three SNPs had a significant effect on the
occurrence of MNBN cell frequency.
