Katiyar S K, Agarwal R, Mukhtar H
Department of Dermatology, University Hospitals of Cleveland, Case Western Reserve University, Ohio 44106.
Cancer Res. 1993 Nov 15;53(22):5409-12.
Progression of benign tumors to malignant cancer is critical since cancerous lesions are capable of metastatic spread and eventually causing death. Inhibitors of the conversion process, therefore, would likely be useful as cancer chemopreventive agents. In this study, we assessed the protective effect of topical application of a polyphenolic fraction isolated from green tea (GTP) against spontaneous as well as benzoyl peroxide (BPO)- and 4-nitroquinoline-N-oxide (4-NQO)-enhanced malignant conversion of chemically induced skin papillomas in SENCAR mice. Papillomas were induced in SENCAR mice by topical application of 7,12-dimethylbenz(a)anthracene as a tumor-initiating agent followed by twice a week application of 12-O-tetradecanoylphorbol-13-acetate as a tumor-promoting agent. Beginning at the 20th week, when papilloma yield was stabilized, enhanced malignant conversion was achieved by twice weekly topical application of either BPO or 4-NQO, whereas spontaneous malignant conversion was associated with topical application of acetone. In these protocols, preapplication of GTP (6 mg/animal) 30 min prior to skin application of acetone, BPO, or 4-NQO resulted in 14, 31, and 29% protection, respectively, in terms of percentage of mice with carcinomas, and 20, 35, and 43% protection in terms of number of carcinomas/mouse. In these experiments, a BPO- and 4-NQO-enhanced rate of malignant conversion was also found to be decreased significantly by the skin application of GTP; however, such effects of GTP were less profound in the cases of spontaneous malignant conversion. The results of this study suggest that, in addition to its chemopreventive effects against tumor initiation and promotion stages of multistage carcinogenesis, green tea also possesses significant protective effects against tumor progression, specifically tumor progression induced by BPO and 4-NQO.
良性肿瘤向恶性癌症的进展至关重要，因为癌性病变能够发生转移扩散并最终导致死亡。因此，这种转化过程的抑制剂可能作为癌症化学预防剂发挥作用。在本研究中，我们评估了局部应用从绿茶中分离出的多酚组分（GTP）对SENCAR小鼠化学诱导的皮肤乳头瘤自发以及由过氧化苯甲酰（BPO）和4-硝基喹啉-N-氧化物（4-NQO）增强的恶性转化的保护作用。通过局部应用7,12-二甲基苯并(a)蒽作为肿瘤启动剂，随后每周两次应用12-O-十四酰佛波醇-13-乙酸酯作为肿瘤促进剂，在SENCAR小鼠中诱导乳头瘤。从第20周开始，当乳头瘤产量稳定时，通过每周两次局部应用BPO或4-NQO实现增强的恶性转化，而自发恶性转化与局部应用丙酮有关。在这些方案中，在皮肤应用丙酮、BPO或4-NQO前30分钟预先应用GTP（6毫克/动物），就患有癌的小鼠百分比而言，分别产生了14%、31%和29%的保护作用，而就每只小鼠的癌数量而言，产生了20%、35%和43%的保护作用。在这些实验中，还发现通过皮肤应用GTP可显著降低BPO和4-NQO增强的恶性转化率；然而，GTP的这种作用在自发恶性转化的情况下不太显著。本研究结果表明，除了对多阶段致癌作用的肿瘤起始和促进阶段具有化学预防作用外，绿茶对肿瘤进展，特别是由BPO和4-NQO诱导的肿瘤进展也具有显著的保护作用。
