Cigarette smoke-induced transgenerational alterations in genome stability in cord blood of human F1 offspring.

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 F1 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 F1 offspring via exposures of the fetus in utero or the paternal germline. Moreover, the identification of transgenerational DNA alterations in the unexposed F1 offspring of smoking-exposed fathers supports the claim that cigarette smoke is a human germ cell mutagen.

• Authors: Julian Laubenthal, Olga Zlobinskaya, Krzysztof Poterlowicz, Adolf Baumgartner, Michal R Gdula, Eleni Fthenou, Maria Keramarou, Sarah J Hepworth, Jos C S Kleinjans, Frederik-Jan van Schooten, Gunnar Brunborg, Roger W Godschalk, Thomas E Schmid, Diana Anderson
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 26 Issue 10 Pg. 3946-56 (Oct 2012) ISSN: 1530-6860 [Electronic] United States
• PMID: 22730438 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cotinine

Topics

• Adolescent
• Adult
• Comet Assay
• Cotinine (urine)
• DNA Damage (drug effects, genetics)
• Female
• Fetal Blood (metabolism)
• Genomic Instability (drug effects, genetics)
• Humans
• Infant, Newborn
• Male
• Maternal Exposure (adverse effects)
• Multivariate Analysis
• Pregnancy
• Smoking (adverse effects)
• Young Adult