Plutonium-catalyzed oxidative DNA damage in the absence of significant alpha-particle decay

Plutonium is considered to be a carcinogen because it emits alpha particles that may result in the irradiation of stem cell population. In the present study we show that plutonium can also catalyze reactions that induce hydroxyl radicals in the absence of significant alpha-particle irradiation. Using the low specific activity isotope, 242Pu, experiments were performed under conditions in which chemical generation of hydroxyl radicals was expected to exceed the radiolytic generation by one hundred thousand-fold. The results showed that markers of oxidative DNA base damage, thymine glycol and 8-oxoguanine could be induced from plutonium-catalyzed reactions of hydrogen peroxide and ascorbate similarly to those occurring in the presence of iron catalysts. Plutonium-242, as a neutralized nitrate in phosphate buffer, was 4.8-fold more efficient than iron at catalyzing the oxidation of ascorbate at pH 7. The results suggest that plutonium complexes could participate in reactions at pH 7 that induce oxidative stress--a significant tumor-promoting factor in generally accepted models of carcinogenesis.