Genetic susceptibility of newborn daughters to oxidative stress
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Genetic susceptibility of newborn daughters to oxidative stress. / Decordier, Ilse; De Bont, Kelly; De Bock, Kirsten; Mateuca, Raluca; Roelants, Mathieu; Ciardelli, Roberta; Haumont, Dominique; Knudsen, Lisbeth E; Kirsch-Volders, Micheline.
In: Toxicology Letters, Vol. 172, No. 1-2, 2007, p. 68-84.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Genetic susceptibility of newborn daughters to oxidative stress
AU - Decordier, Ilse
AU - De Bont, Kelly
AU - De Bock, Kirsten
AU - Mateuca, Raluca
AU - Roelants, Mathieu
AU - Ciardelli, Roberta
AU - Haumont, Dominique
AU - Knudsen, Lisbeth E
AU - Kirsch-Volders, Micheline
N1 - Keywords: Adult; Antioxidants; Cells, Cultured; DNA Damage; DNA Glycosylases; DNA-Binding Proteins; Female; Genotype; Humans; Hydrogen Peroxide; Infant, Newborn; Leukocytes, Mononuclear; Methylenetetrahydrofolate Reductase (NADPH2); Micronucleus Tests; Mutagens; Oxidative Stress; Phenotype; Pilot Projects; Polymorphism, Genetic; Pregnancy; Risk Assessment; Risk Factors; Xeroderma Pigmentosum Group D Protein
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
U2 - 10.1016/j.toxlet.2007.05.014
DO - 10.1016/j.toxlet.2007.05.014
M3 - Journal article
C2 - 17614221
VL - 172
SP - 68
EP - 84
JO - Toxicology Letters
JF - Toxicology Letters
SN - 0378-4274
IS - 1-2
ER -
ID: 17264879