Khan W A, Wang Z Y, Athar M, Bickers D R, Mukhtar H
Department of Dermatology, University Hospitals of Cleveland, Case Western Reserve University, OH.
Cancer Lett. 1988 Sep-Oct;42(1-2):7-12. doi: 10.1016/0304-3835(88)90232-7.
The effect of pretreatment of skin of Sencar mice with topically applied tannic acid, quercetin and green tea polyphenols (GTP) on the skin tumor initiating activity of (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE-2) has been evaluated. The animals were pretreated with the plant phenols (tannic acid and quercetin (3000 nmol) or GTP 24 mg/mouse) for 7 days after which they received a single topical application of 200 nmol of BPDE-2 as the initiating agent. Beginning 7 days following initiation animals received twice weekly applications of 3.24 nmol of 12-O-tetradecanoyl phorbol-13-acetate (TPA). Tannic acid and GTP afforded significant protection against skin tumor induction. These inhibitory effects were verified both by prolongation of the latency period and subsequent development of tumors. Quercetin, on the other hand, afforded only moderate protection. Each phenolic compound was found to be highly effective in accelerating the disappearance of BPDE-2 from aqueous medium. Our results suggest that tannic acid and GTP have substantial potential for protecting against the skin tumorigenic response to BPDE-2 and the mechanism of inhibition may involve inactivation of the reactive carcinogenic moiety.
已评估了对Sencar小鼠皮肤局部应用鞣酸、槲皮素和绿茶多酚(GTP)预处理对(±)-7β,8α-二羟基-9α,10α-环氧-7,8,9,10-四氢苯并[a]芘(BPDE-2)皮肤肿瘤启动活性的影响。用植物酚(鞣酸和槲皮素(3000 nmol)或GTP 24 mg/小鼠)对动物进行预处理7天,之后它们接受单次局部应用200 nmol的BPDE-2作为启动剂。在启动后7天开始,动物每周接受两次3.24 nmol的12-O-十四烷酰佛波醇-13-乙酸酯(TPA)的应用。鞣酸和GTP对皮肤肿瘤诱导提供了显著的保护作用。这些抑制作用通过潜伏期的延长和随后肿瘤的发生得到了验证。另一方面,槲皮素仅提供了适度的保护。发现每种酚类化合物在加速BPDE-2从水性介质中消失方面都非常有效。我们的结果表明,鞣酸和GTP在预防对BPDE-2的皮肤致瘤反应方面具有巨大潜力,并且抑制机制可能涉及活性致癌部分的失活。