Effects of aging and caloric restriction on I-compounds in liver, kidney and white blood cell DNA of male Brown-Norway rats.
Rodent tissues display species-, strain-, sex- and tissue-specific adduct-like DNA modifications termed I-compounds, which increase with age, are modulated by diet and are presumably derived from indigenous metabolic intermediates. We have explored whether I-compounds are affected by caloric restriction, which is known to extend life span and retard age-related degenerative and neoplastic diseases. Male Brown-Norway rats were fed NIH-31 diet ad libitum (AL). Calorically restricted (CR) rats received 60% of AL consumption, starting at 3.5 months. DNA was analyzed by 32P-postlabeling at 1, 4, 8, 12, 16 and 24 months of age in liver, kidney and white blood cells. I-compounds in AL liver and kidney exhibited complex tissue specific profiles; I-compound levels increased with age, plateaued between 8 and 18 months depending on tissue and diet and were 8.7 (liver) and 27.4 (kidney) modifications in 10(8) nucleotides at 24 months, thereby exceeding the corresponding 1-month values by 3.7- and 16.6-fold. CR resulted in similar profiles but did not diminish age-related increases, rather I-compound levels in CR liver and kidney were increased by about 70% and 30% versus age-matched AL rats. White blood cells exhibited few I-compounds and at low levels; age-related increases were small overall but more pronounced in CR rats. Higher I-compound levels in CR animals, which were presumably a consequence of metabolic effects elicited by CR, thus correlated with extended life span and, therefore, may be beneficial, in agreement with previous findings showing an association between reduced I-compound levels and hepatocarcinogenesis as well as organ susceptibility to diseases.
Randerath
E
E
Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030.
Hart
R W
RW
Turturro
A
A
Danna
T F
TF
Reddy
R
R
Randerath
K
K
D000375:Aging / Q000378:metabolism*; D000818:Animals; D004247:DNA / Q000097:blood / Q000378:metabolism*; D004032:Diet; D002149:Energy Intake; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D007962:Leukocytes / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D009374:Neoplasms, Experimental / Q000209:etiology; D051381:Rats; D011914:Rats, Inbred BN; D014018:Tissue Distribution
D004247:DNA