The tissue specificity of the age-related changes in alkali-induced DNA-unwinding

To determine if the age-related changes in chromatin digestibility are tissue-specific, fluorometric analysis of the alkali-induced DNA unwinding technique was adapted for soft-tissue chromatin studies. The rate of DNA unwinding in the brain and liver of young Fischer 344 male rats (3 months of age) was significantly greater than the rates measured in middle-aged (15 months) or aged rats (26 months). In contrast, the rate of DNA unwinding in the intestinal epithelium, a continuously replicating tissue, did not significantly vary with age. Although this assay is capable of detecting DNA strand breaks in vivo following N-nitrosodimethylamine administration, the age-related changes could not be attributed to reduced DNA strand lesions in the aged animals. The % double-stranded DNA at time 0 of incubation in alkali was lower in the brain and liver of aged rats indicating that DNA strand breaks may actually increase with aging. These results indicate that proliferative activity of the tissue is an important determinant of age-related changes in chromatin structure.