Concurrent increase of oxidative DNA damage and lipid peroxidation together with mitochondrial DNA mutation in human lung tissues during aging - Smoking enhances oxidative stress on the aged tissues

Although mutation of mitochondrial DNA (mtDNA) in human tissues has been es tablished to associate with intrinsic aging, the impact of environmental fa ctors on the formation and accumulation of mtDNA mutations and oxidative DN A damage in human tissues is poorly understood. We have investigated the le vels of mtDNA with the 4977-bp deletion and A3243G point mutation, oxidativ e DNA damage (indicated by the formation of 8-hydroxy-2'-deoxyguanosine, 8- OH-dG), and lipid peroxides in lung tissues from smokers and nonsmokers of subjects of different ages. The results showed concurrent age-dependent inc rease of the 4977-bp deleted mtDNA (P < 0.001), 8-OH-dG: (P < 0.05), and li pid peroxides (P < 0.05) in the human lung. In the group of subjects above 60 years old, smokers had more extensive DNA damage and lipid peroxidation than did the nonsmokers. However, the levels of mtDNA with the 4977-bp dele tion and A3243G; point mutation in the lung of smokers were not significant ly different from those of the age-matched nonsmokers. Taken together, thes e results suggest that accumulation of mtDNA with the 4977-bp deletion toge ther with oxidative DNA damage and lipid peroxides is associated with aging and that smoking enhances oxidative damage in human lung tissues. (C) 1999 Academic Press.