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Chemopreventive Effects of -Santalol on Skin Tumor Development in CD-1 and SENCAR Mice¹

Departments of Pharmaceutical Sciences, and Chemistry and Biochemistry, South Dakota State University, Brookings, South Dakota 57007

Studies from our laboratory have indicated skin cancer chemopreventive effectsof sandalwood oil in CD-1 mice. The purpose of this investigation was to study the skin cancer chemopreventive effects of -santalol, a principal component of sandalwood oil in CD-1 and SENCAR mice. -Santalol was isolated from sandalwood oil by distillation under vacuum and characterized by nuclear magnetic resonance and gas chromatography-mass spectrometry. Chemopreventive effects of -santalol were determined during initiation and promotion phase in female CD-1 and SENCAR mice. Carcinogenesis was initiated with 7,12-dimethylbenz(a)anthracene and promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA). The effects of -santalol treatment on TPA-induced epidermal ornithine decarboxylase (ODC) activity and ³H-thymidine incorporation in epidermal DNA of CD-1 and SENCAR mice were also investigated. -Santalol treatment during promotion phase delayed the papilloma development by 2 weeks in both CD-1 and SENCAR strains of mice. -Santalol treatment during promotion phase significantly (P < 0.05) decreased the papilloma incidence and multiplicity when compared with control and treatment during initiation phase during 20 weeks of promotion in both CD-1 and SENCAR strains of mice. -Santalol treatment resulted in a significant (P < 0.05) inhibition in TPA-induced ODC activity and incorporation of ³H-thymidine in DNA in the epidermis of both strains of mice. -Santalol significantly prevents papilloma development during promotion phase of 7,12-dimethylbenz(a)anthracene-TPA carcinogenesis protocol in both CD-1 and SENCAR mice, possibly by inhibiting TPA-induced ODC activity and DNA synthesis. -Santalol could be an effective chemopreventive agent for skin cancer. Additional experimental and clinical studies are needed to investigate the chemopreventive effect of -santalol in skin cancer.

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