Typical signature of DNA damage in white blood cells: a pilot study on etheno adducts in Danish mother-newborn child pairs.
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,N(6)-ethenodeoxyadenosine (epsilondA) and 3,N(4)-ethenodeoxycytidine (epsilondC) were measured by our ultrasensitive immunoaffinity (32)P-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 epsilondA and epsilondC levels when expressed per 10(9) 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 epsilondA and epsilondC levels in cord versus maternal blood WBC showed strong positive correlations (R(2) approximately 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 epsilondA and epsilondC 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.
Arab
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Division of Epigenomics, German Cancer Research Center (DKFZ), Heidelberg, Germany. a.khelifa@dkfz.de
Pedersen
M
M
Nair
J
J
Meerang
M
M
Knudsen
L E
LE
Bartsch
H
H
D000447:Aldehydes / Q000378:metabolism; D002648:Child; D018736:DNA Adducts / Q000737:chemistry*; D004249:DNA Damage / Q000502:physiology*; D003839:Deoxyadenosines / Q000097:blood*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000097:blood; D005260:Female; D005312:Fetal Blood; D006801:Humans; D007231:Infant, Newborn; D007962:Leukocytes / Q000378:metabolism*; D015227:Lipid Peroxidation; D010865:Pilot Projects; D011247:Pregnancy
D000447:Aldehydes; D018736:DNA Adducts; D003839:Deoxyadenosines; D003841:Deoxycytidine; C032221:1,N(6)-ethenodeoxyadenosine; C032222:3,N(4)-ethenodeoxycytidine; C027576:4-hydroxy-2-nonenal