OXIDATIVE DAMAGE TO SKELETAL-MUSCLE DNA FROM PATIENTS WITH MITOCHONDRIAL ENCEPHALOMYOPATHIES

To estimate the oxidative damage to skeletal muscle DNA in mitochondri al encephalomyopathies, we studied the amount of 8-hydroxy-deoxyguanos ine (8-OH-dG) and the localization of superoxide dismutase (SOD) in th e skeletal muscles of patients with progressive external ophthalmopleg ia (PEO) or Kearns-Sayre syndrome (KSS). The molar ratio of 8-OH-dG/de oxyguanosine in skeletal muscle from PEO or KSS patients was significa ntly higher than the control value. The ratio from patients with polym yositis or Duchenne's muscular dystrophy was not significantly elevate d. Immunohistochemical staining for both Mn-SOD and Cu,Zn-SOD showed p ronounced staining in the subsarcolemmal and intermyofibrillar regions of cytochrome-oxidase-negative ragged red fibers of KSS or PEO muscle s. Our findings suggest that overproduction of 8-OH-dG and mitochondri al dysfunction with gene deletions are associated with each other in m uscle cells of patients with PEO or KSS, and that free radicals may pl ay an important role in the pathophysiology of mitochondrial encephalo myopathies.