Genetic susceptibility of newborn daughters to oxidative stress.

2.50
Hdl Handle:
http://hdl.handle.net/10146/19093
Title:
Genetic susceptibility of newborn daughters to oxidative stress.
Authors:
Decordier, Ilse; De Bont, Kelly; De Bock, Kirsten; Mateuca, Raluca; Roelants, Mathieu; Ciardelli, Roberta; Haumont, Dominique; Knudsen, Lisbeth E; Kirsch-Volders, Micheline
Abstract:
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.
Citation:
Toxicol. Lett. 2007, 172 (1-2):68-84.
Publisher:
Elsevier
Journal:
Toxicology Letters
Issue Date:
30-Jul-2007
URI:
http://hdl.handle.net/10146/19093
DOI:
10.1016/j.toxlet.2007.05.014
PubMed ID:
17614221
Additional Links:
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TCR-4NTJH0X-9&_user=1843694&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000055040&_version=1&_urlVersion=0&_userid=1843694&md5=1db1a55c9c1f158b720851a60e76be7e
Type:
Article
Language:
en
ISSN:
0378-4274
Sponsors:
This work was supported by ChildrenGenoNetwork (QLRT-2001-02198), a concerted action operating within the European Union 5th Framework Program, Key action 4: “Environment and Health”; NewGeneris (FOOD-CT-2005-016320-2) an integrated research project operating within the European Union 6th Framework Program, Priority 5: “Food Quality and Safety”; ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence (FOOD-CT-2005-513943) operating within the same EU Framework Program, Priority 5; and by a matching EU fund from VUB (OZR 1102).
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorDecordier, Ilse-
dc.contributor.authorDe Bont, Kelly-
dc.contributor.authorDe Bock, Kirsten-
dc.contributor.authorMateuca, Raluca-
dc.contributor.authorRoelants, Mathieu-
dc.contributor.authorCiardelli, Roberta-
dc.contributor.authorHaumont, Dominique-
dc.contributor.authorKnudsen, Lisbeth E-
dc.contributor.authorKirsch-Volders, Micheline-
dc.date.accessioned2008-02-25T10:44:44Z-
dc.date.available2008-02-25T10:44:44Z-
dc.date.issued2007-07-30-
dc.identifier.citationToxicol. Lett. 2007, 172 (1-2):68-84.en
dc.identifier.issn0378-4274-
dc.identifier.pmid17614221-
dc.identifier.doi10.1016/j.toxlet.2007.05.014-
dc.identifier.urihttp://hdl.handle.net/10146/19093-
dc.description.abstractA 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.en
dc.description.sponsorshipThis work was supported by ChildrenGenoNetwork (QLRT-2001-02198), a concerted action operating within the European Union 5th Framework Program, Key action 4: “Environment and Health”; NewGeneris (FOOD-CT-2005-016320-2) an integrated research project operating within the European Union 6th Framework Program, Priority 5: “Food Quality and Safety”; ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence (FOOD-CT-2005-513943) operating within the same EU Framework Program, Priority 5; and by a matching EU fund from VUB (OZR 1102).en
dc.language.isoenen
dc.publisherElsevieren
dc.relation.urlhttp://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TCR-4NTJH0X-9&_user=1843694&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000055040&_version=1&_urlVersion=0&_userid=1843694&md5=1db1a55c9c1f158b720851a60e76be7een
dc.subjectchildren susceptibilityen
dc.subjectDNA repairen
dc.subjectgenetic polymorphismsen
dc.subjectoxidative stressen
dc.subject.meshAdult-
dc.subject.meshAntioxidants-
dc.subject.meshCells, Cultured-
dc.subject.meshDNA Damage-
dc.subject.meshDNA Glycosylases-
dc.subject.meshDNA-Binding Proteins-
dc.subject.meshFemale-
dc.subject.meshGenotype-
dc.subject.meshHumans-
dc.subject.meshHydrogen Peroxide-
dc.subject.meshInfant, Newborn-
dc.subject.meshLeukocytes, Mononuclear-
dc.subject.meshMethylenetetrahydrofolate Reductase (NADPH2)-
dc.subject.meshMicronucleus Tests-
dc.subject.meshMutagens-
dc.subject.meshOxidative Stress-
dc.subject.meshPhenotype-
dc.subject.meshPilot Projects-
dc.subject.meshPolymorphism, Genetic-
dc.subject.meshPregnancy-
dc.subject.meshRisk Assessment-
dc.subject.meshRisk Factors-
dc.subject.meshXeroderma Pigmentosum Group D Protein-
dc.titleGenetic susceptibility of newborn daughters to oxidative stress.en
dc.typeArticleen
dc.identifier.journalToxicology Lettersen

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