Dhawan D, Balasubramanian S, Amonkar A J, Singh N
Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029 and Cancer Research Institute, Parel Mumbai, India.
Carcinogenesis. 1999 Jun;20(6):997-1003. doi: 10.1093/carcin/20.6.997.
The chemopreventive effect of topical application of 4'-demethyl epipodophyllotoxin (DMEP), an antimitotic agent, on a two-stage skin carcinogenesis model in Swiss Albino mice induced by 9, 10-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) was investigated. Two topical applications with 0.24% DMBA over 1 week, followed later by 5 nmol of TPA twice weekly produced 100% incidence of tumors in these animals by 18 weeks. Treatment of animals with DMEP (until the end of the experiment), 30 min before TPA treatment, significantly reduced the tumor incidence, tumor volume and the conversion efficiency of papillomas to squamous cell carcinomas. The tumor formation and growth was also delayed by DMEP pre-treatment. Application of DMEP protected against the losses provoked in levels of glutathione and activity of catalase and superoxide dismutase in skin and liver of animals by the application of DMBA/TPA. Thus, DMEP might possibly be exerting its chemopreventive activity by acting as an antioxidant.
研究了抗有丝分裂剂4'-去甲基表鬼臼毒素（DMEP）局部应用于由9,10-二甲基苯并[a]蒽（DMBA）/12-O-十四烷酰佛波醇-13-乙酸酯（TPA）诱导的瑞士白化小鼠两阶段皮肤癌发生模型的化学预防作用。在1周内用0.24% DMBA进行两次局部应用，随后每周两次用5 nmol TPA处理，到18周时这些动物的肿瘤发生率达到100%。在TPA处理前30分钟用DMEP处理动物（直至实验结束），可显著降低肿瘤发生率、肿瘤体积以及乳头状瘤向鳞状细胞癌的转化效率。DMEP预处理还延迟了肿瘤的形成和生长。应用DMEP可防止DMBA/TPA处理引起的动物皮肤和肝脏中谷胱甘肽水平、过氧化氢酶和超氧化物歧化酶活性的降低。因此，DMEP可能通过作为抗氧化剂发挥其化学预防活性。
