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α-檀香醇对CD-1和SENCAR小鼠皮肤肿瘤发生的化学预防作用。

Chemopreventive effects of alpha-santalol on skin tumor development in CD-1 and SENCAR mice.

作者信息

Dwivedi Chandradhar, Guan Xiangming, Harmsen Wendy L, Voss Alison L, Goetz-Parten Dawn E, Koopman Erin M, Johnson Kelly M, Valluri Hima B, Matthees Duane P

机构信息

Department of Pharmaceutical Sciences, South Dakota State University, Brookings 57007, USA.

出版信息

Cancer Epidemiol Biomarkers Prev. 2003 Feb;12(2):151-6.

Abstract

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 alpha-santalol, a principal component of sandalwood oil in CD-1 and SENCAR mice. alpha-Santalol was isolated from sandalwood oil by distillation under vacuum and characterized by nuclear magnetic resonance and gas chromatography-mass spectrometry. Chemopreventive effects of alpha-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 alpha-santalol treatment on TPA-induced epidermal ornithine decarboxylase (ODC) activity and (3)H-thymidine incorporation in epidermal DNA of CD-1 and SENCAR mice were also investigated. alpha-Santalol treatment during promotion phase delayed the papilloma development by 2 weeks in both CD-1 and SENCAR strains of mice. alpha-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. alpha-Santalol treatment resulted in a significant (P < 0.05) inhibition in TPA-induced ODC activity and incorporation of (3)H-thymidine in DNA in the epidermis of both strains of mice. alpha-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. alpha-Santalol could be an effective chemopreventive agent for skin cancer. Additional experimental and clinical studies are needed to investigate the chemopreventive effect of alpha-santalol in skin cancer.

摘要

我们实验室的研究表明檀香油对CD-1小鼠具有皮肤癌化学预防作用。本研究的目的是研究檀香醇(檀香油的主要成分)对CD-1和SENCAR小鼠的皮肤癌化学预防作用。檀香醇通过真空蒸馏从檀香油中分离出来,并通过核磁共振和气相色谱-质谱联用进行表征。在雌性CD-1和SENCAR小鼠的启动和促进阶段测定檀香醇的化学预防作用。用7,12-二甲基苯并(a)蒽启动致癌过程,并用12-O-十四烷酰佛波醇-13-乙酸酯(TPA)促进。还研究了檀香醇处理对TPA诱导的CD-1和SENCAR小鼠表皮鸟氨酸脱羧酶(ODC)活性以及表皮DNA中(3)H-胸腺嘧啶掺入的影响。在促进阶段进行檀香醇处理使CD-1和SENCAR品系小鼠的乳头瘤发生延迟2周。在促进阶段进行檀香醇处理与对照以及在CD-1和SENCAR品系小鼠20周促进期的启动阶段进行处理相比,显著(P<0.05)降低了乳头瘤发生率和多发性。檀香醇处理导致两种品系小鼠表皮中TPA诱导的ODC活性以及DNA中(3)H-胸腺嘧啶掺入受到显著(P<0.05)抑制。檀香醇在7,12-二甲基苯并(a)蒽-TPA致癌方案的促进阶段显著预防CD-1和SENCAR小鼠的乳头瘤发生,可能是通过抑制TPA诱导的ODC活性和DNA合成。檀香醇可能是一种有效的皮肤癌化学预防剂。需要进一步的实验和临床研究来研究檀香醇在皮肤癌中的化学预防作用。

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