Endogenous deoxyribonucleic Acid (DNA) damage in human tissues: a comparison of ethenobases with aldehydic DNA lesions.
Two types of endogenous DNA lesions, ethenobases [1,N(6)-ethenoadenine (epsilonA), 3,N(4)-ethenocytosine (epsilonC)] and aldehydic DNA lesions (ADLs), were measured in several tissues (liver, lung, kidney, colon, colon mucosa, cerebellum, and gray and white matter of the cerebrum) obtained postmortem during autopsy examinations of 12 individuals (6 males, 6 females; ages, 58-87 years). Issues relating to changes in levels of DNA damage with disease and after death were addressed. The extent of DNA damage in autopsy samples was not associated with the length of the postmortem interval and was similar to levels observed in surgery samples, suggesting that endogenous, steady-state levels of etheno adducts and of ADLs are relatively stable during the hours immediately after death. In this limited series of samples, and with a few possible exceptions, the disease status before death was not associated with increased endogenous DNA damage in the affected tissue. DNA ethenobases were lowest in the cerebellum (median molar ratios: epsilonA/A = 1.0 x 10(-8); epsilonC/C = 1.9 x 10(-8)) and highest in the gray matter (epsilonA/A = 2.9 x 10(-8); epsilonC/C = 4.8 x 10(-8)) and white matter (epsilonA/A = 2.4 x 10(-8); epsilonC/C = 5.2 x 10(-8)) of the cerebrum. In other tissues, median values were 1.2-1.9 x 10(-8) for epsilonA/A and 2.0-3.3 x 10(-8) for epsilonC/C. There was a good correlation between the levels of epsilonA and epsilonC (r = 0.80, P < 0.0001). Levels of ADLs were similar in the liver, lung, kidney, and white matter of the cerebrum (median values: 5.7-7.9 ADLs/10(6) nucleotides), higher in the colon (11.3 x 10(-6)) and gray matter of the cerebrum (9.0 x 10(-6)) and lower in the cerebellum (3.7 x 10(-6)). There was no correlation between levels of ethenobases and amounts of ADLs (epsilonA versus ADLs: r = 0.12, P = 0.33; epsilonC versus ADLs: r = 0.024, P = 0.85). Although there was an interindividual variability in the extent of endogenous DNA damage (4-fold for epsilonA and epsilonC, 2-fold for ADLs), which may be determined, in part, by the capacity to repair DNA and may be related to the pathology or treatment of the patients, these results suggest that the cerebrum contains higher endogenous DNA damage than the other tissues. These data are in line with previous studies showing that brain tissues are more susceptible to oxidative stress and lipid peroxidation than other tissues.
Barbin
Alain
A
International Agency for Research on Cancer, Lyon, France. barbin@iarc.fr
Ohgaki
Hiroko
H
Nakamura
Jun
J
Kurrer
Michael
M
Kleihues
Paul
P
Swenberg
James A
JA
D000368:Aged; D000369:Aged, 80 and over; D000447:Aldehydes; D001344:Autopsy; D001921:Brain / Q000473:pathology; D018736:DNA Adducts; D004249:DNA Damage; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D014018:Tissue Distribution
D000447:Aldehydes; D018736:DNA Adducts