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- Title
Cigarette smoke-induced transgenerational alterations in genome stability in cord blood of human F1 offspring.
- Authors
Laubenthal, Julian; Zlobinskaya, Olga; Poterlowicz, Krzysztof; Baumgartner, Adolf; Gdula, Michal R.; Fthenou, Eleni; Keramarou, Maria; Hepworth, Sarah J.; Kleinjans, Jos C. S.; Van Schooten, Frederik-Jan; Godschalk, Roger W.; Schmid, Thomas E.; Anderson, Diana; Brunborg, Gunnar
- Abstract
The relevance of preconceptional and prenatal toxicant exposures for genomic stability in offspring is difficult to analyze in human populations, because gestational exposures usually cannot be separated from preconceptional exposures. To analyze the roles of exposures during gestation and conception on genomic stability in the offspring, stability was assessed via the Comet assay and highly sensitive, semiautomated confocal laser scans of γH2AX foci in cord, maternal, and paternal blood as well as spermatozoa from 39 families in Crete, Greece, and the United Kingdom. With use of multivariate linear regression analysis with backward selection, preconceptional paternal smoking (% tail DNA: P> 0.032; γH2AX foci: P>0.018) and gestational maternal (% tail DNA: P>0.033) smoking were found to statistically significantly predict DNA damage in the cord blood of Fl offspring. Maternal passive smoke exposure was not identified as a predictor of DNA damage in cord blood, indicating that the effect of paternal smoking may be transmitted via the spermatozoal genome. Taken together, these studies reveal a role for cigarette smoke in the induction of DNA alterations in human Fl offspring via exposures of the fetus in utero or the paternal germline. Moreover, the identification of transgenerational DNA alterations in the unexposed Fl offspring of smoking-exposed fathers supports the claim that cigarette smoke is a human germ cell mutagen.
- Subjects
POISONS; DNA damage; GERM cells; MUTAGENS; SPERMATOZOA; CORD blood
- Publication
FASEB Journal, 2012, Vol 26, Issue 10, p3946
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.11-201194