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International Journal of Toxicology
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Oral Toxicity of 1,2-Dithiole-3-Thione, a Potential Cancer Chemopreventive Agent, in the Rat

Alan P. Brown

Toxicology Research Laboratory, Department of Pharmacology, University of Illinois at Chicago, Chicago, Illinois, USA

Robert L. Morrissey

Pathology Associates International, Chicago, Illinois, USA

Thomas A. Tolhurst

Drug Disposition Research Laboratory, Department of Pharmaceutics, University of Illinois at Chicago, Chicago, Illinois, USA

James A. Crowell

Division of Cancer Prevention and Control, National Cancer Institute, NIH, Rockville, Maryland, USA

Barry S. Levine

Toxicology Research Laboratory, Department of Pharmacology, University of Illinois at Chicago, Chicago, Illinois, USA

This study examined the toxicity of 1,2-dithiole-3-thione (D3T) in rats following 14 days of daily oral (gavage) administration. D3T, an extensive inducer of hepatic phase II drug-metabolizing enzymes, has demonstrated cancer preventive efficacy in rodent models of tumorigenesis and is a candidate drug for cancer prevention. Male and female CD rats (5/sex/dose group) received D3T at dose levels of 0 (corn oil vehicle control), 2, 6, 20, and 60 mg/kg/day. Oral administration of D3T for 14 days at 20 mg/kg/day resulted in decreased activity, lethargy, rough coat, and piloerection, and toxicologically significant lesions in the stomach, characterized by apoptotic necrosis and hyperplasia of the glandular mucosa. Administration of D3T at 60 mg/kg/day produced anemia in females, decreased body weight gain in males, and increased vacuolation of adrenal cortical cells. Increased liver weights, vacuolation of hepatocytes, and serum chemistry changes, indicative of altered liver function, were observed at 6 mg/kg/day, which were likely due to a pharmacologic effect of D3T on the liver and not considered to be toxicologically significant. Under the conditions of the study, the no-observed-adverse effect level (NOAEL) was 6 mg/kg/day.

Key Words: Anemia • Cancer Chemoprevention • Chemopreventive Agent • Dithiolethione • Gastric Toxicity • Liver

International Journal of Toxicology, Vol. 19, No. 6, 375-381 (2000)
DOI: 10.1080/109158100750058721
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This article has been cited by other articles:


Home page
 Molecular Cancer TherapeuticsHome page
Y. Zhang and R. Munday
Dithiolethiones for cancer chemoprevention: where do we stand?
Mol. Cancer Ther., November 1, 2008; 7(11): 3470 - 3479.
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