Induction of DT-diaphorase by anticarcinogenic sulfur compounds in mice.
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.
A M
AM
Benson
P B
PB
Barretto
J S
JS
Stanley
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003600:Cytosol / Q000201:enzymology; D001728:Dicumarol / Q000494:pharmacology; D004220:Disulfides / Q000494:pharmacology*; D004221:Disulfiram / Q000494:pharmacology*; D004050:Ditiocarb / Q000494:pharmacology; D004790:Enzyme Induction; D005260:Female; D005982:Glutathione Transferase / Q000096:biosynthesis; D017879:Isothiocyanates; D051379:Mice; D008861:Microsomes / Q000201:enzymology; D011808:Quinone Reductases / Q000032:analysis / Q000096:biosynthesis*; D013861:Thiocyanates / Q000494:pharmacology*; D013871:Thiones
D000970:Antineoplastic Agents; D004220:Disulfides; D017879:Isothiocyanates; D013861:Thiocyanates; D013871:Thiones; D001728:Dicumarol; C031403:benzyl isothiocyanate; D004050:Ditiocarb; D011808:Quinone Reductases; D005982:Glutathione Transferase; C000171:dixanthogen; D004221:Disulfiram