1,2-dithiole-3-thione and its structural analogue oltipraz are potent inhibitors of dibenz.
Dithiolethiones are currently one of the most promising classes of cancer chemopreventive agents that exhibit antitumorigenic properties at numerous organ sites against several classes of carcinogens. In the current study, we examined the effects of 2 dithiolethiones, 1,2-dithiole-3-thione (D3T) and its structural analogue oltipraz, on DNA adduction induced by the potent mammary carcinogen dibenzo-[a,l]pyrene (DBP) in vivo. Female Sprague-Dawley rats were provided dietary D3T and oltipraz (500 ppm each) for I week followed by a single intragastric dose of DBP (8 micromol/kg body weight) and killed 5 days later. D3T inhibited DBP-DNA adduction from 78% to 82% in all tissues examined, while oltipraz was equally effective in the lung and liver but less effective in the mammary glands, inhibiting DBP-DNA adduction by nearly 60%. These data coupled with their broad anti-tumor specificity support the use of D3T and oltipraz as cancer-preventive agents in clinical trials.
Smith
W A
WA
Graduate Center for Toxicology, University of Kentucky Medical Center, Lexington 40536-0305, USA.
Arif
J M
JM
Gupta
R C
RC
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001580:Benzopyrenes / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D002845:Chromatography; D018736:DNA Adducts; D005260:Female; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000378:metabolism; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013871:Thiones / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D001580:Benzopyrenes; D018736:DNA Adducts; D011719:Pyrazines; D013871:Thiones; D013876:Thiophenes; C026209:oltipraz; C041517:dibenzo(a,l)pyrene; C049325:1,2-dithiol-3-thione