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.
BACKGROUND
Oxygen free radicals have been hypothesized to play an important role in the process of aging.


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.
Ishchenko
Alexander
A
Novosibirsk Institute of Bioorganic Chemistry, Novosibirsk, Russia.
Sinitsyna
Olga
O
Krysanova
Zhanna
Z
Vasyunina
Elena A
EA
Saparbaev
Murat
M
Sidorkina
Olga
O
Nevinsky
Gregory A
GA
D000375:Aging; D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology; D045647:DNA Glycosylases; D043382:DNA-Formamidopyrimidine Glycosylase; D004591:Electrophoresis, Polyacrylamide Gel; D005609:Free Radicals; D006026:Glycoside Hydrolases / Q000494:pharmacology; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019271:Hypoxanthine / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism; D009699:N-Glycosyl Hydrolases / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D013997:Time Factors; D014498:Uracil / Q000494:pharmacology; D051981:Uracil-DNA Glycosidase; D014508:Urea / Q000494:pharmacology
D005609:Free Radicals; D019271:Hypoxanthine; C024829:8-hydroxyguanine; D014498:Uracil; D006147:Guanine; D014508:Urea; D006026:Glycoside Hydrolases; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D051981:Uracil-DNA Glycosidase; C035336:DNA-deoxyinosine glycosidase; D043382:DNA-Formamidopyrimidine Glycosylase