Pro-oxidative, genotoxic and cytotoxic properties of uranyl ions.

It is demonstrated that hydroxyl radicals and hydrogen peroxide are formed under the action of uranyl ions in aqueous solutions containing no reducing agents. In the presence of uranyl ions, formation of 8-oxoguanine in DNA and long-lived protein radicals are observed in vitro. It is shown that the pro-oxidant properties of uranyl at micromolar concentrations mostly result from the physico-chemical nature of the compound rather than its radioactive decay. Uranyl ions lead to damage in DNA and proteins causing death of HEp-2 cells by necrotic pathway. It is revealed that the uranyl ions enhance radiation-induced oxidative stress and significantly increase a death rate of mice exposed to sublethal doses of X-rays.