Age-dependent increase of 8-oxoguanine-, hypoxanthine-, and uracil- DNA glycosylase activities in liver extracts from OXYS rats with inherited overgeneration of free radicals and Wistar rats.
Alexander Ishchenko, Olga Sinitsyna, Zhanna Krysanova, Elena Vasyunina, Murat Saparbaev, Olga Sidorkina, Gregory Nevinsky
Med Sci Monit 2003; 9(1): BR16-24
BACKGROUND: Oxygen free radicals have been hypothesized to play an important role in the process of aging. MATERIAL/METHODS: To investigate the correlation between oxidative stress and accumulation of DNA damage we determined age-dependent levels of activities eliminating 8-oxoguanine, hypoxanthine and uracil from DNA in liver cells from OXYS rats, which are characterized by inherited overgeneration of free radicals, in comparison with those of control Wistar rats. RESULTS: A pronounced difference in the specificity of mitochondrial and nuclear 8-oxoguanine DNA glycosylase/AP lyase activities were revealed in both cases. Our results suggest the induction of an 8-oxoG-, uracil- and hypoxanthine-specific repair pathway with age in both types of rats. The levels of 8-oxoguanine DNA glycosylase/AP lyase activities in nuclear extracts from both strains of rats are comparable and approximately tenfold higher than in mitochondrial extracts. On the contrary, 8-oxoguanine DNA glycosylase/AP lyase activity in OXYS mitochondrial extracts was remarkably higher than that from old Wistar rats, and a significant increase of this activity occurs earlier in OXYS than in Wistar rats. CONCLUSIONS: Our results are consistent with the shorter life-span of OXYS rats, and with the mitochondrial theory of aging, which postulates that the accumulation of DNA damage in mitochondrial genomes leads to mitochondrial dysfunction and accelerates the process of aging.
Keywords: Glycoside Hydrolases - pharmacology, Guanine - analogs & derivatives, Hypoxanthine - pharmacology, Uracil - pharmacology