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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.
Insights
Four sulfur compounds increased DT-diaphorase activity, a protective enzyme, in mice. This enzyme
Area of Science:
- Biochemistry
- Toxicology
- Cancer Research
Background:
- DT-diaphorase is a key enzyme in detoxifying harmful quinones and quinoneimines.
- Its role in limiting free-radical formation suggests a protective function against cellular damage.
- Understanding enzyme induction by dietary compounds is crucial for chemoprevention strategies.
Purpose of the Study:
- To investigate the effects of four anticarcinogenic sulfur compounds on DT-diaphorase activity in mice.
- To determine which organs and cellular fractions (cytosol, microsomes) show altered enzyme levels.
- To assess the dose-dependency of these effects, particularly for bisethylxanthogen.
Main Methods:
- Dietary administration of bisethylxanthogen, disulfiram, sodium diethyldithiocarbamate, and benzylisothiocyanate to female CD-1 mice.
- Analysis of DT-diaphorase specific activity in cytosolic and microsomal fractions from various organs (lung, kidney, liver, etc.).
- Evaluation of enzyme induction at different dietary concentrations (0.5%, 0.05%).
Main Results:
- All four sulfur compounds significantly increased DT-diaphorase specific activity in multiple organs' cytosol.
- Bisethylxanthogen, disulfiram, and benzylisothiocyanate elevated fore-stomach cytosolic DT-diaphorase.
- Bisethylxanthogen and benzylisothiocyanate also increased microsomal DT-diaphorase activity; bisethylxanthogen showed effects even at a tenfold lower dose.
Conclusions:
- Dietary administration of these four sulfur compounds effectively induces DT-diaphorase activity in various mouse organs.
- The induction of this protective enzyme likely contributes to the observed anticarcinogenic effects of these compounds.
- Bisethylxanthogen demonstrates potent induction of DT-diaphorase at low dietary concentrations, highlighting its potential chemopreventive value.