Selenium (Se) compounds that form the selonate anion (RSe-) either by their reduction with thiols or as a result of metabolism such as demethylation of methlyated Se compounds redox cycle and generate superoxide and other reactive oxygen species and are toxic. Presently known Se compounds to redox cycle in vitro include selenodiglutathione and numerous diselenides. Dimethlydiselenide when tested in vitro at 25°C with reduced glutathione and lucigenin generated superoxide (1.01 CL units/μmole/30sec) in a dose dependent manner. Superoxide production was sustainable for at least 5 minutes. In comparison, dimethyldisulfide under the same experimental conditions produced minimal amounts of superoxide (<0.02 CL units/μmole/30sec) which was sustainable for less than sixty seconds. Thus dimethyldiselenide redox cycled and generated superoxide which could be quenched in a dose dependent manner with superoxide dismutase. Dimethyldisulfide did not generate significant amounts of superoxide. Both dimethlydiselenide and dimethyldisulfide are considered toxic. The comparatively low toxicity of dimethyldisulfide may be due to its inability to generate superoxide. The significance of the ability of dimethyldiselenide in the anionic seleonate form (CH3Se-) to generate superoxide is that the two rather non-toxic chemopreventive forms of selenium, selenomenthionine (JAMA (1996) 276: 1957-1963) and Se-methylselenocysteine (Cancer Res. (1991) 51: 595-600) are fully capable of release of a selenoate anion (CH3Se-) following metabolism in vivo. This beta elimination reaction may occur preferentially in cancer cells compared to normal cells and may account for the anticancer activity of selenomethionine and Se-methylselenocysteine.
|State||Published - Mar 20 1998|