Carcinogenesis Advance Access originally published online on November 26, 2008
Carcinogenesis 2009 30(2):282-285; doi:10.1093/carcin/bgn264
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Typical signature of DNA damage in white blood cells: a pilot study on etheno adducts in Danish mother–newborn child pairs
1 Division of Epigenomics
2 Division of Toxicology and Cancer Risk Factors (C010), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
3 Department of Environmental Health, Institute of Public Health, University of Copenhagen, 1014 K Copenhagen, Denmark
* To whom correspondence should be addressed. Tel: +49 6221 423337; Fax: +49 6221 423359; Email: a.khelifa{at}dkfz.de
The impact of DNA damage commonly thought to be involved in chronic degenerative disease causation is particularly detrimental during fetal development. Within a multicenter study, we analyzed 77 white blood cell (WBC) samples from mother–newborn child pairs to see if imprinting of DNA damage in mother and newborn shows a similar pattern. Two adducts 1,N6-ethenodeoxyadenosine (
dA) and 3,N4-ethenodeoxycytidine (dC) were measured by our ultrasensitive immunoaffinity 32P-post-labeling method. These miscoding etheno-DNA adducts are generated by the reaction of lipid peroxidation (LPO) end products such as 4-hydroxy-2-nonenal with DNA bases. Mean dA and dC levels when expressed per 109 parent nucleotides in WBC-DNA from cord blood were 138 and 354, respectively; in maternal WBC-DNA, the respective values were 317 and 916. Thus, the DNA-etheno adduct levels were reliably detectable and about two times lower in child cord blood, the difference being significant at P < 0.0004. Analysis of dA and dC levels in cord versus maternal blood WBC showed strong positive correlations (R2 
0.9, P < 0.00001). In conclusion, LPO-induced DNA damage arising from endogenous reactive aldehydes in WBC of both mother and newborn can be reliably assessed by dA and dC as biomarkers. The high correlation of etheno adduct levels in mother and child WBC suggests that a typical signature of DNA damage is induced similarly in fetus and mother. Prospective cohort studies have to reveal whether these two WBC-DNA adducts could serve as risk indicator for developing hematopoietic cancers and other disorders later in life.
Abbreviations: dA, 1,N6-ethenodeoxyadenosine; dC, 3,N4-ethenodeoxycytidine; LPO, lipid peroxidation; M1dG, 3-(2-deoxy-D-erythro-pentofuranosyl)pyrimido[1,2-]purin-10(3H)-one; WBC, white blood cell
Received September 19, 2008; revised November 13, 2008; accepted November 18, 2008.