Katiyar S K, Perez A, Mukhtar H
Department of Dermatology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Clin Cancer Res. 2000 Oct;6(10):3864-9.
Cancer chemopreventive effects of polyphenols from green tea (GTP) in mouse models of photocarcinogenesis are established. The present study is extended from mouse model to human system in vivo to determine the effect of topical application of GTP to human individuals against UV light-induced DNA damage in the form of cyclobutane pyrimidine dimers (CPDs) in the skin. UVB-induced CPDs were detected by immunohistochemical technique using monoclonal antibodies to thymine dimers. With the gradual increase in UVB dose, both erythema response and CPD formation in the skin was increased. GTP treatment inhibited both UVB-induced erythema response as well as CPD formation. Topical treatment with GTP (approximately 1 mg/cm2 of skin area) 20 min before human buttock skin (sun-protected site) exposure to UVB inhibited CPD formation in epidermis by 81, 70, 60, and 60% at 0.5, 1.0, 2.0, and 4.0 minimal erythema dose of UV exposure, respectively. Treatment of human skin with varying doses of GTP (1-4 mg/2.5 cm2 of skin area) before a single dose of UVB exposure (4.0 minimal erythema dose) decreased dose dependently the formation of UVB-induced CPDs in both epidermis and dermis. The inhibition of UVB-induced CPDs by GTP treatment may be, at least in part, responsible for the inhibition of photocarcinogenesis. Our data suggest that GTP may be used as a novel chemopreventive candidate and possible strategy to reduce UV-induced skin cancer risk in the human population.
绿茶多酚(GTP)在光致癌小鼠模型中的癌症化学预防作用已得到证实。本研究从小鼠模型扩展到人体系统,以确定局部应用GTP对人体个体皮肤中环丁烷嘧啶二聚体(CPD)形式的紫外线诱导DNA损伤的影响。使用针对胸腺嘧啶二聚体的单克隆抗体,通过免疫组织化学技术检测UVB诱导的CPD。随着UVB剂量逐渐增加,皮肤中的红斑反应和CPD形成均增加。GTP处理可抑制UVB诱导的红斑反应以及CPD形成。在人体臀部皮肤(防晒部位)暴露于UVB前20分钟,用GTP(约1mg/cm²皮肤面积)局部处理,在0.5、1.0、2.0和4.0最小红斑剂量的紫外线暴露下,分别抑制表皮中CPD形成81%、70%、60%和60%。在单次UVB暴露(4.0最小红斑剂量)前,用不同剂量的GTP(1 - 4mg/2.5cm²皮肤面积)处理人体皮肤,可剂量依赖性地降低UVB诱导的表皮和真皮中CPD的形成。GTP处理对UVB诱导的CPD的抑制作用可能至少部分地解释了其对光致癌作用的抑制。我们的数据表明,GTP可作为一种新型化学预防剂,并可能成为降低人群中紫外线诱导皮肤癌风险的策略。