Induction of DT-diaphorase by anticarcinogenic sulfur compounds in mice

Abstract

The effects of the dietary administration of four anticarcinogenic sulfur compounds on the activity of DT-diaphorase, a protective enzyme in quinone and quinoneimine detoxification, have been investigated in female CD-1 mice. Bisethylxanthogen, disulfiram, sodium diethyldithiocarbamate, and benzylisothiocyanate, administered at 0.5% of the diet (by weight) for 14 days, each induced significant increases in DT-diaphorase specific activities in cytosol fractions of lung, kidney, urinary bladder, proximal small intestine, and colon. Cytosolic DT-diaphorase of the fore-stomach was elevated in response to bisethylxanthogen, disulfiram, and benzylisothiocyanate. The increases in cytosolic DT-diaphorase activities in organs of mice fed 0.5% bisethylxanthogen were similar in magnitude to those observed previously in response to 0.75% butylated hydroxyanisole. Liver cytosol DT-diaphorase specific activity was enhanced sevenfold by 0.5% bisethylxanthogen, twofold by 0.5% benzylisothiocyanate, and 2.6-fold by 1% disulfiram but was not significantly increased by disulfiram or sodium diethyldithiocarbamate at 0.5% of the diet. Diets containing 0.5% bisethylxanthogen or 0.5% benzylisothiocyanate also elevated microsomal DT-diaphorase specific activities in several organs. Even at the tenfold-lower concentration of 0.05% of the diet, bisethylxanthogen induced significant increases in DT-diaphorase specific activities in cytosol fractions of liver, lung, kidney, and small intestine and in liver and kidney microsomes. The protective function of DT-diaphorase in limiting free-radical formation and oxidative damage to cells suggests that the induction of this enzyme contributes to the anticarcinogenic effects of the four sulfur compounds studied.