Katiyar S K, Mohan R R, Agarwal R, Mukhtar H
Department of Dermatology, Case Western Reserve University, Cleveland, OH 44106-5028, USA.
Carcinogenesis. 1997 Mar;18(3):497-502. doi: 10.1093/carcin/18.3.497.
We earlier showed that a polyphenolic fraction isolated from green tea (GTP) affords protection against tumor promotion and tumor progression in SENCAR mouse skin. The present study was designed to further evaluate the protective effect of GTP against the induction and subsequent progression of papillomas to squamous cell carcinomas (SCCs) in experimental protocols where papillomas were developed with a low or high probability of their malignant conversion. Topical application of GTP (6 mg/animal) 30 min prior to that of 12-O-tetradecanoylphorbol-13-acetate (TPA) either once a week for 5 weeks (high risk TPA protocol) or once a week for 20 weeks (low risk TPA protocol) or mezerein (MEZ) twice a week for 20 weeks (high risk MEZ protocol) in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated mouse skin resulted in significant protection against skin tumor promotion in terms of tumor incidence (32-60%), multiplicity (49-63%) and tumor volume/mouse (73-90%) at the termination of the experiment at 20 weeks. In three separate malignant progression experiments when papilloma yield in DMBA-initiated and TPA or MEZ promoted low and high risk protocols was stabilized at 20 weeks, animals were divided into two subgroups. These animals were either topically treated twice weekly with acetone (0.2 ml/animal, spontaneous malignant conversion group) or with GTP (6 mg/animal in 0.2 ml acetone) for an additional period of 31 weeks. During these treatment regimens, all suspected carcinomas were recorded and each one was verified histopathologically either at the time when tumor-bearing mouse died/moribund or at the termination of the experiment at 51 weeks. GTP resulted in significant protection against the malignant conversion of papillomas to SCC in all the protocols employed. At the termination of the experiment at 51 weeks, these protective effects were evident in terms of mice with carcinomas (35-41%), carcinomas per mouse (47-55%) and percent malignant conversion of papillomas to carcinomas (47-58%). The kinetics of malignant conversion suggest that a subset of papillomas formed in the early phase of tumor promotion in all the protocols had a higher probability of malignant conversion into SCCs because all the positive control groups (acetone treated) produced nearly the same number of carcinomas (33-38 in a group of 20 animals) at the end of the progression period. In the GTP-treated group of animals the number of carcinomas formed was less (14-20 in a group of 20 animals), which shows the ability of GTP to protect against the malignant conversion of papillomas of higher probability of malignant conversion to SCCs. The results of this study suggest that irrespective of the risk involved, GTP may be highly useful in affording protection against skin cancer risk.
我们之前的研究表明，从绿茶中分离出的多酚组分（GTP）可在SENCAR小鼠皮肤中预防肿瘤促进和肿瘤进展。本研究旨在进一步评估GTP在实验方案中对乳头状瘤诱导及随后向鳞状细胞癌（SCC）进展的保护作用，在这些实验方案中，乳头状瘤发生恶性转化的概率有高有低。在7,12 - 二甲基苯并[a]蒽（DMBA）引发的小鼠皮肤上，在每周一次共5周（高风险TPA方案）或每周一次共20周（低风险TPA方案）给予12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）之前30分钟局部应用GTP（6mg/只动物），或每周两次共20周（高风险MEZ方案）给予豆寇酰佛波醇乙酯（MEZ），在实验20周结束时，在肿瘤发生率（32 - 60%）、多发性（49 - 63%）和每只小鼠肿瘤体积（73 - 90%）方面，对皮肤肿瘤促进有显著的保护作用。在三个单独的恶性进展实验中，当DMBA引发且TPA或MEZ促进的低风险和高风险方案中的乳头状瘤产量在20周时稳定后，将动物分为两个亚组。这些动物要么每周两次局部用丙酮（0.2ml/只动物，自发恶性转化组）处理，要么用GTP（6mg/只动物溶于0.2ml丙酮）再处理31周。在这些治疗方案期间，记录所有疑似癌瘤，并在荷瘤小鼠死亡/濒死时或在51周实验结束时对每一个进行组织病理学验证。在所有采用的方案中，GTP对乳头状瘤向SCC的恶性转化有显著的保护作用。在51周实验结束时，这些保护作用在患有癌瘤的小鼠（35 - 41%）、每只小鼠的癌瘤数（47 - 55%）以及乳头状瘤向癌瘤的恶性转化百分比（47 - 58%）方面很明显。恶性转化的动力学表明，在所有方案中肿瘤促进早期形成的一部分乳头状瘤有更高的概率恶性转化为SCC，因为所有阳性对照组（丙酮处理组）在进展期结束时产生的癌瘤数量几乎相同（一组20只动物中为33 - 38个）。在GTP处理的动物组中形成的癌瘤数量较少（一组20只动物中为14 - 20个），这表明GTP能够预防具有较高恶性转化为SCC概率的乳头状瘤的恶性转化。本研究结果表明，无论涉及何种风险，GTP在预防皮肤癌风险方面可能非常有用。
