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 PI-enhanced version of the P-32-postlabeling assay for bulky covalently modified nucleotides. A reproducible pattern of three P-32-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 less-than-or-equal-to 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.