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

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

1. Julian Laubenthal*,
2. Olga Zlobinskaya†,
3. Krzysztof Poterlowicz‡,
4. Adolf Baumgartner*,§,
5. Michal R. Gdula∥,
6. Eleni Fthenou¶,
7. Maria Keramarou¶,
8. Sarah J. Hepworth#,
9. Jos C. S. Kleinjans**,
10. Frederik-Jan van Schooten††,
11. Gunnar Brunborg‡‡,
12. Roger W. Godschalk††,
13. Thomas E. Schmid† and
14. Diana Anderson*,²

+ Author Affiliations

1. ^*Division of Biomedical Sciences and
2. ^‡Centre of Skin Sciences, School of Life Sciences, University of Bradford, Bradford, UK;
3. ^†Department of Radiation Therapy, Klinikum Rechts der Isar, Munich Technical University, Munich, Germany;
4. ^§Department of Paediatric Cardiology, Cardiac Centre, University of Leipzig, Leipzig, Germany;
5. ^∥Department of Dermatology, School of Medicine, University of Boston, Boston, Massachusetts, USA;
6. ^¶Department of Social Medicine, School of Medicine, University of Crete, Crete, Greece;
7. ^#Division of Epidemiology, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, UK;
8. ^**Department of Toxicogenomics and
9. ^††Department of Toxicology, University of Maastricht, Maastricht, The Netherlands; and
10. ^‡‡Department of Chemical Toxicology, Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo, Norway

1. ↵2Correspondence: School of Life Sciences, University of Bradford, Richmond Rd., Bradford BD7 1DP, UK. E-mail: d.anderson1@bradford.ac.uk

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.—Laubenthal, J., Zlobinskaya, O., Poterlowicz, K., Baumgartner, A., Gdula, M. R., Fthenou, E., Keramarou, M., Hepworth, S. J., Kleinjans, J. C. S., van Schooten, F.-J., Brunborg, G., Godschalk, R. W., Schmid, T. E., Anderson, D. Cigarette smoke-induced transgenerational alterations in genome stability in cord blood of human F1 offspring.

• toxicants
• DNA damage
• male germline
• transmission
• germ cell mutagen

• Received January 3, 2012.
• Accepted June 5, 2012.

• © FASEB