DEFECTIVE REPAIR OF OXIDATIVE DAMAGE IN THE MITOCHONDRIAL-DNA OF A XERODERMA-PIGMENTOSUM GROUP-A CELL-LINE

Recent evidence has linked mitochondrial DNA (mtDNA) damage to several disease processes, including cancer and aging. An important source of such damage is reactive oxygen species. These molecules can be genera ted endogenously via the electron transport system or may arise from a host of exogenous sources. It has been reported that extracts from ce lls of individuals with xeroderma pigmentosum group A (XP-A) do not re pair some types of oxidative DNA damage. The current experiments were designed to determine whether there is a correlation between the inade quate repair of oxidatively damaged nuclear DNA in XP-A cells and the capacity of such cells to repair similar damage to their mtDNA. The ab ility of karyotypically normal human fibroblasts (WI-38) and XP-A fibr oblasts to repair alloxan-generated oxidative damage to nuclear and mt DNA was assessed using a quantitative Southern blot method in conjunct ion with the repair enzymes endonuclease III and formamidopyrimidine D NA glycosylase. The data indicate that both nuclear and mtDNA repair o f each damage type investigated is more efficient in the WI-38 cells. These findings suggest a similarity between the process(es) used to re pair oxidative damage to nuclear and mtDNA in that both are inhibited by the defect in XP-A.