Susceptibility of DNA to oxidative stressors in young and aging mice.
The changes that accompany aging may be a result of oxidative damage to DNA that accumulates as a result of aging and age-related illnesses. Furthermore, a higher susceptibility is thought to be more common among elderly than young individuals. In the present study, we examined the severity of DNA damage caused by carbon tetrachloride (CCl4) and H2O2 in cells from young (2 month old) and older (14 month old) mice using both in vivo and in vitro exposures. CCl(4) is known to generate radical oxidative species (ROS) throughout its biotransformation in the liver. Therefore, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxdGuo) was quantified in liver DNA obtained from young and older mice treated with CCl4. In addition, DNA single-strand breaks were measured by the Comet assay in primary lung fibroblasts cultured from young and older mice and treated in vitro with H2O2. Intracellular ROS production and mitochondrial enzyme activity were determined in parallel. 8-oxodGuo levels were significantly higher in older mouse liver DNA than younger, and increased significantly with CCl4 treatment. When the basal DNA damage was subtracted, the net damage was almost equal for both. In addition, untreated cells cultured from older mice had significantly greater levels of strand breaks than cells derived from young mice. H2O2 increased the level of damage in both cell cultures. Our findings indicate that the DNA damage observed in older animals probably results from the accumulation of endogenous damage with age, perhaps due to insufficient repair, which enhances the injury caused by exposure to the toxic agents.
Departamento de Ciencias de la Salud, División de Ciencias Biológicas y de la Salud, UAM-Iztapalapa, A.P. 55-535, México, D.F. 09340, México.
Norma E
NE
López-Diazguerrero
Armando
A
Luna-López
María C
MC
Gutiérrez-Ruiz
Alejandro
A
Zentella
Mina
M
Königsberg
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000375:Aging / Q000187:drug effects*; D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D020552:Comet Assay; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D006861:Hydrogen Peroxide / Q000633:toxicity*; D008099:Liver / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013053:Spectrophotometry; D013778:Tetrazolium Salts; D013844:Thiazoles
D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; D000080242:8-Hydroxy-2'-Deoxyguanosine; D006861:Hydrogen Peroxide; D002251:Carbon Tetrachloride; C022616:thiazolyl blue; D003849:Deoxyguanosine