Baskaran Nagarethinam, Manoharan Shanmugam, Karthikeyan Sekar, Prabhakar Murugaraj Manoj
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalai nagar, Tamil Nadu, India.
Asian Pac J Cancer Prev. 2012;13(10):5273-9. doi: 10.7314/apjcp.2012.13.10.5273.
The aim of the present study was to investigate the chemopreventive effect of coumarin against 7, 12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis by monitoring tumor incidence and histopathological changes as well as by analyzing the status of biochemical markers (lipid peroxidation, enzymatic and non-enzymatic antioxidants, phase I and phase II detoxification enzymes). Oral squamous cell carcinomas were induced in the buccal pouch of Syrian golden hamsters by painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. We noted 100% tumor formation with marked abnormalities in the biomarkers status in hamsters treated with DMBA alone. Oral administration of coumarin at a dose of 100 mg/kg body weight (bw) to DMBA treated hamsters completely prevented the tumor formation as well as restored the status of biochemical variables. The results of the present study thus suggest that the chemopreventive effect of coumarin is probably due to its anti-lipid peroxidative potential and modulating effect on carcinogen detoxification agents in favor of the excretion of ultimate carcinogenic metabolites of DMBA during DMBA-induced hamster buccal pouch carcinogenesis.
本研究的目的是通过监测肿瘤发生率和组织病理学变化，以及分析生化标志物（脂质过氧化、酶促和非酶促抗氧化剂、I 期和 II 期解毒酶）的状态，研究香豆素对 7,12-二甲基苯并[a]蒽（DMBA）诱导的仓鼠颊囊癌变的化学预防作用。通过每周三次用 0.5% DMBA 的液体石蜡溶液涂抹叙利亚金仓鼠的颊囊，持续 14 周，诱导口腔鳞状细胞癌。我们注意到，单独用 DMBA 处理的仓鼠中肿瘤形成率为 100%，生物标志物状态有明显异常。对经 DMBA 处理的仓鼠口服剂量为 100 mg/kg 体重的香豆素，完全阻止了肿瘤形成，并恢复了生化变量的状态。因此，本研究结果表明，香豆素的化学预防作用可能归因于其抗脂质过氧化潜力以及对致癌物解毒剂的调节作用，有利于在 DMBA 诱导的仓鼠颊囊癌变过程中排出 DMBA 的最终致癌代谢产物。
