Environmental-gene Interactions Of Polycyclic Aromatic Hydrocarbons Exposure To Maternal And Infant DNA Oxidative Damage

Objective: Through the detection of DNA oxidative damage in pregnant women and neonates and the analysis of repair enzyme gene polymorphism,explore the polycyclic aromatic hydrocarbon(PAHs)exposure to maternal and infant DNA oxidative damage and XPC,XPD,ERCC1 polymorphism Sexual relationship,clarify the role of gene polymorphism in the repair of DNA damage caused by PAHs and its correlation in maternal and infant bodies,and reveal the environment-gene interaction and its mechanism.Methods: During the heating period and non-heating period,100 pregnant women and 100 newborns included in a hospital in Urumqi were taken as the research objects for epidemiological investigation and biological sample collection.The concentration of 8-hydroxy-2'deoxyguanosin(8-OHdG)in maternal plasma,urine and neonatal umbilical cord blood serum was detected by enzyme-linked immunosorbent assay(ELISA).Maternal and neonatal repair enzyme genes XPCLys939 Gln,XPDLys751Gln,ERCC1C118 T single nucleotide polymorphism detection using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)method.Combined with the data of the level of PAHs exposure in this group,the relationship between DNA oxidative damage and XPC,XPD,ERCC1 polymorphisms caused by PAH exposure during pregnancy was analyzed.Results: 1.The 8-OHdG in maternal plasma,urine,and neonatal cord blood serum collected during the heating period were higher than those during the non-heating period(P<0.05).2.Pearson correlation analysis showed that 8-OHdG in maternal plasma was positively correlated with 8-OHdG in urine(P<0.05),and positively correlated with 8-OHdG in neonatal serum(P<0.05).8-OHdG was also positively correlated with neonatal serum 8-OHdG(P<0.05).Multiple linear stepwise regression analysis showed that plasma 8-OHdG concentration was related to maternal passive smoking.Correlation analysis showed that the total PAHs concentration in maternal blood was positively correlated with plasma 8-OHdG(P<0.05)and also positively correlated with neonatal serum 8-OHdG(P<0.05).There was a positive correlation between the total PAHs in neonatal blood and 8-OHdG in their serum(P<0.05).3.XPCLys939 Gln gene polymorphism is associated with maternal plasma 8-OHdG(P<0.05).There was no correlation with maternal urine and neonatal serum 8-OHdG(P>0.05).XPCLys939 Gln locus CC homozygous mutation genotype maternal plasma 8-OHdG levels were higher than pregnant women carrying AA wild type and AC variant heterozygous type.XPDLys751 Gln gene polymorphism was associated with maternal urine 8-OHdG(P<0.05).It was not associated with 8-OHdG in maternal plasma and neonatal serum(P>0.05).The maternal 8-OHdG concentration in the CC homozygous mutant genotype of XPDLys751 Gln locus was higher than that of pregnant women carrying AA wild type and AC variant heterozygous type.ERCC1C118 T gene polymorphism was associated with 8-OHdG in maternal plasma,urine and neonatal serum(P<0.05).Plasma 8-OHdG levels in ERCC1C118 T loci with TT homozygous mutation genotypes were higher than those in pregnant women carrying CC wild type and CT variant heterozygous type.Maternal 8-OHdG levels in ERCC1C118 T locus homozygous mutant TT genotypes were higher than those in pregnant women carrying CC wild type.The serum level of 8-OHdG in the neonatal homozygous mutant genotype of TT at ERCC1C118 T locus was higher than that of CT variant heterozygous in pregnant women.4.Analysis of environmental-gene interactions revealed that there were interactions between maternal and neonatal exposure levels of different PAHs and XPCLys939 Gln,ERCC1C118T gene polymorphisms on maternal urine,plasma,and neonatal 8-OHdG(P<0.05).However,different levels of PAHs exposure and XPDLys751 Gln gene polymorphism did not interact with maternal plasma 8-OHdG(P>0.05),and there was an interaction between maternal urine and neonatal serum 8-OHdG(P<0.05).Conclusion: Maternal and neonatal DNA damage in heating period was higher than that in non-heating period.Passive smoking during pregnancy may to some extent cause maternal and neonatal DNA damage.Exposure of polycyclic aromatic hydrocarbons to oxidative damage to maternal and infant DNA may have varying degrees of impact.Oxidative damage to maternal and infant DNA is related to the polymorphisms of the repair enzymes XPC,XPD,ERCC1.Polycyclic aromatic hydrocarbon exposure has environmental-gene interaction effects on maternal and infant DNA oxidative damage.