Urinary excretion of DNA repair products correlates with metabolic rates as well as with maximum life spans of different mammalian species

Using recently developed methodology, which includes HPLC prepurification followed by GC/MS with isotope dilution, we analyzed urinary excretion of possible repair products of oxidative DNA damage-8-oxo-7,8-dihydroguanine (8-oxoGua), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), and 5-(hydroxymethyl)uracil (5-HMUra)-in mammalian species that substantially differ in metabolic rate and longevity, namely, mice, rats, rabbits, dogs, pigs, and humans. We found highly significant, positive correlations between specific metabolic rates of the animals studied and their excretion rates for all the modifications analyzed with respective r values for the lesions of (8-oxoGua) r =.891, p <.01; (8-oxodG) r =.998, p <.001; and (5-HMUra) r =.949, p <.005. However, only 8-oxoGua significantly correlates negatively with maximum life span (MLSP) (r =.928, p <.01). Despite substantial differences in MLSP between humans and pigs (120 and 27 years, respectively), the rates of excretion of all measured modifications were very similar. The urinary levels of all measured modifications found in our study for mouse and humans account respectively for about 34,000 and 2800 repaired events per average cell, per 24 It. It is therefore possible that the high metabolic rate in mice (or other short-lived animals) may be responsible for severe everyday oxidative DNA insults that may be accumulated faster than in long-lived species. (C) 2004 Elsevier Inc. All rights reserved.