ATTENUATION OF AGE-DEPENDENT OXIDATIVE DAMAGE TO DNA AND PROTEIN IN BRAIN-STEM OF TG CU ZN SOD MICE/

Age-dependent accumulation of oxidative DNA and protein damage in brai nstem and striatum was assessed in normal and transgenic (tg) mice whi ch overexpress human Cu/Zn superoxide dismutase (h-SOD1). A marker of oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine (oxo(8)dG), was meas ured at 3, 12, and 18 months of age in control and tg mice. Cu/Zn SOD, but not MnSOD, activities in brainstems and striata from tg mice were increased compared to controls at all ages. At 18 months, oxo8dG leve ls were increased by 58% in brainstem and by 21% in striatum of contro l mice. In the tg mice, brainstem and striatal oxo8dG levels were incr eased to a lesser extent than in the corresponding controls. Protein o xidation (carbonyl content), was increased by 59% at 18 months in cont rol brainstem, but not in striatum, and the increase was significantly attenuated in the tg mice. In summary, oxidative damage to DNA and pr otein increased with age in brainstem land to a lesser extent in stria tum), and augmented Cu/Zn SOD activity modified the extent of DNA and protein damage. (C) 1998 Elsevier Science Inc.