Age-dependent increases of DNA adducts (I-compounds) in human and rat brain DNA.
Brain DNA from 20 humans ranging in age from neonatal to 100 years was analyzed by the nuclease P1-enhanced version of the 32P-postlabeling assay for bulky covalently modified nucleotides. A reproducible pattern of three 32P-labeled spots was obtained by thin-layer chromatography followed by autoradiography. Two of these spots increased with age (Mann-Whitney U-test; P < 0.001; comparison of ages < or = 60 years and ages > 60 years). Thus, these spots met the definition of I-compounds. Rat brain DNA exhibited the same two I-spots, whose intensities also increased with animal age (1, 4, and 10 months). In humans, considerable individual variation of brain I-compound levels was observed, especially at ages > 60 years, presumably reflecting environmental, life-style, or genetic factors. This variation was not noted for brain DNA of laboratory rats. Thus, human brain DNA undergoes progressive covalent modifications with aging.
Randerath
K
K
Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030.
Putman
K L
KL
Osterburg
H H
HH
Johnson
S A
SA
Morgan
D G
DG
Finch
C E
CE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002675:Child, Preschool; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D051381:Rats; D017207:Rats, Sprague-Dawley
D004247:DNA