Genetic susceptibility of newborn daughters to oxidative stress.
A central question in risk assessment is whether newborns' susceptibility to mutagens is different from that of adults. Therefore we investigated whether genotype and/or the DNA strand break repair phenotype in combination with the MN assay would allow estimation of the relative sensitivity of a newborn as compared to his mother for oxidative DNA damage. We compared the in vitro genetic susceptibility for H2O2 in PBMC of 17 mother-newborn daughter pairs taking into account genotypes for relevant DNA repair (hOGG1, XRCC1, XRCC3, XPD) and folate metabolism (MTHFR) polymorphisms. After in vitro challenge with H2O2 the repair capacity was assessed by the Comet assay and chromosome/genome mutations by the cytokinesis-block MN assay. No statistically significant differences were found between mothers and their newborn daughters either for initial DNA damage or for residual DNA damage. Mothers showed higher background frequencies of MN as compared to their newborn daughters, due to the age factor. This was confirmed by significantly higher frequencies of MN observed in mothers versus newborn daughters for several genotypes. No genotype with a significant effect on DNA repair capacity in newborns was identified. Concerning MN frequencies, however, newborns carrying the variant XRCC3(241) genotype might be at higher risk for the induction of MN by oxidative stress. Multivariate analysis revealed a significant protective effect of maternal antioxidant supplementation during pregnancy against oxidative DNA damage in newborns in terms of MN frequencies. However, these conclusions might not be extrapolable to other types of DNA damage and need confirmation in a study on a larger population.
Decordier
Ilse
I
Laboratory of Cell Genetics, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium. idecordi@vub.ac.be
De Bont
Kelly
K
De Bock
Kirsten
K
Mateuca
Raluca
R
Roelants
Mathieu
M
Ciardelli
Roberta
R
Haumont
Dominique
D
Knudsen
Lisbeth E
LE
Kirsch-Volders
Micheline
M
D000328:Adult; D000975:Antioxidants / Q000494:pharmacology; D002478:Cells, Cultured; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D006861:Hydrogen Peroxide / Q000009:adverse effects*; D007231:Infant, Newborn; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000201:enzymology; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D015162:Micronucleus Tests; D009153:Mutagens / Q000009:adverse effects*; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D010641:Phenotype; D010865:Pilot Projects; D011110:Polymorphism, Genetic; D011247:Pregnancy; D018570:Risk Assessment; D012307:Risk Factors; D000076105:X-ray Repair Cross Complementing Protein 1; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics
D000975:Antioxidants; D004268:DNA-Binding Proteins; D009153:Mutagens; D000076105:X-ray Repair Cross Complementing Protein 1; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human; D006861:Hydrogen Peroxide; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human