Inhibition of DMBA/croton oil-induced two-stage mouse skin carcinogenesis by diphenylmethyl selenocyanate.

Abstract

Selenium, an essential micronutrient, is associated with antioxidant functions, physiological defence mechanisms against different diseases including several types of cancers. Search for new selenium compounds with more chemopreventive activities and lesser toxicities are in progress. In the present study, the antioxidative roles of a synthetic organoselenium compound, diphenylmethyl selenocyanate, were evaluated against 7,12-dimethylbenz(a)anthracene (DMBA)/croton oil-induced two-stage mouse skin carcinogenesis model. The compound was administered orally in carcinogen-induced mice in two different non-toxic doses: 2 mg/kg body weight and 3 mg/kg body weight. Significant inhibition in the incidence of papilloma formation (58-80%) as well as in the cumulative number of papilloma per papilloma-bearing mouse were observed in the treated groups as compared with the carcinogen control group. The compound was also found to significantly upregulate different phase II detoxifying enzymes in liver cytosol such as glutathione-S-transferase (P<0.01), catalase (P<0.01) and superoxide dismutase (SOD) (P<0.01) when measured after 15 days and also after 12 weeks of first DMBA treatment. Lipid peroxidation measured as the thiobarbituric acid reactive substances in liver microsomes was significantly inhibited (P<0.05) in a dose-dependent manner by diphenylmethyl selenocyanate. Thus the compound exerts its chemopreventive activity by reducing papilloma formation during chemically induced carcinogenesis, which in turn, may be through modulating the level of lipid peroxidation and phase II detoxifying enzyme system at the doses evaluated.

• Authors: R K Das, S Ghosh, A Sengupta, S Das, S Bhattacharya
• Journal: European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) (Eur J Cancer Prev) Vol. 13 Issue 5 Pg. 411-7 (Oct 2004) ISSN: 0959-8278 [Print] England
• PMID: 15452454 (Publication Type: Journal Article)

Chemical References

• Anticarcinogenic Agents
• Antioxidants
• Carcinogens
• Dermatologic Agents
• Organoselenium Compounds
• diphenylmethyl selenocyanate
• 9,10-Dimethyl-1,2-benzanthracene
• Croton Oil

Topics

• 9,10-Dimethyl-1,2-benzanthracene (administration & dosage, toxicity)
• Administration, Oral
• Animals
• Anticarcinogenic Agents (pharmacology)
• Antioxidants (pharmacology)
• Carcinogens (administration & dosage, toxicity)
• Croton Oil (administration & dosage, toxicity)
• Dermatologic Agents (administration & dosage, toxicity)
• Female
• Lipid Peroxidation
• Mice
• Organoselenium Compounds (pharmacology)
• Papilloma (chemically induced, prevention & control)
• Skin Neoplasms (chemically induced, prevention & control)