Cigarette smoke-induced transgenerational alterations in genome stability in cord blood of human F1 offspring.
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.
Centre of Skin Sciences, School of Life Sciences, University of Bradford, Richmond Rd., Bradford BD7 1DP, UK.
Julian
J
Laubenthal
Olga
O
Zlobinskaya
Krzysztof
K
Poterlowicz
Adolf
A
Baumgartner
Michal R
MR
Gdula
Eleni
E
Fthenou
Maria
M
Keramarou
Sarah J
SJ
Hepworth
Jos C S
JC
Kleinjans
Frederik-Jan
FJ
van Schooten
Gunnar
G
Brunborg
Roger W
RW
Godschalk
Thomas E
TE
Schmid
Diana
D
Anderson
D000293:Adolescent; D000328:Adult; D020552:Comet Assay; D003367:Cotinine / Q000652:urine; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D042822:Genomic Instability / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D015999:Multivariate Analysis; D011247:Pregnancy; D012907:Smoking / Q000009:adverse effects*; D055815:Young Adult
D003367:Cotinine