Induction of phase II enzymes by 3H-1,2-dithiole-3-thione: dose-response study in rats

Derivatives of 3H-1,2-dithiole-3-thione (D3T) are known to protect against a variety of chemical carcinogens. There is evidence that this chemoprotective effect depends, at least in part, on the ability of these compounds to increase tissue activities of phase II detoxification enzymes. In the present study, D3T was dosed to rats at daily doses of between 0.98 and 125 micromol/kg/day for 5 days. The activity of two phase II enzymes, quinone reductase and glutathione S-transferase, were then assayed in the liver, spleen, kidneys, lungs, heart, urinary bladder, forestomach, glandular stomach, duodenum, jejunum, ileum, caecum and colon plus rectum of the animals. D3T was particularly effective in increasing enzyme activities in the stomach and duodenum, with significant effects being recorded at a dose-level of only 0.98 micromol/kg/day. At slightly higher dose-levels, increases were recorded in other segments of the small and large intestine and in the urinary bladder. D3T caused enlargement of the liver, kidneys, stomach and intestinal tract of the animals at the higher dose-levels, but no other toxic effects were recorded. D3T is a very effective inducer of phase II enzymes, showing significant effects at lower dose-levels than any other compound for which dose-response data are available. The inductive potency of D3T makes it a most promising candidate for use as a chemoprotective agent.