Modulation of Oxidative Damage by Tea Polyphenols

描述(由申请人提供) 本研究项目的主要目的是研究调制 绿茶多酚对小鼠肝细胞癌的抑制作用 高危人群中的氧化损伤。黄曲霉毒素引起的氧化损伤 体内的活性氧在人体内起着重要作用 慢性乙型/丙型肝炎引起的肝癌 病毒和饮食中黄曲霉毒素的暴露。8-羟基-2‘- 脱氧鸟苷，一种氧化DNA损伤的生物标志物，在乙肝患者中增加 病毒表面抗原阳性和接触黄曲霉毒素的人以及黄曲霉毒素- 治疗过的动物。饮食中的抗氧化剂是癌症的重要组成部分 已被证明能有效靶向致癌物质的调节剂 生物标记物，包括氧化损伤，在高危人群中。 在各种已确定的饮食相关抗氧化剂中，绿茶及其 多酚已被证明是安全和高效的抑制一种 多种致癌物诱导的氧化损伤、诱变和 体外生物测定和体内动物模型中的肿瘤发生。这位将军 这一提议背后的假设是绿茶多酚具有 对黄曲霉毒素所致氧化应激或损伤的保护作用 乙肝病毒对黄曲霉毒素的调控机制 代谢和氧化的DNA损伤。具体目标包括：(1) 测定绿茶多酚的抗氧化作用对细胞的抑制作用 安徽省某社区居民尿液中8-羟基-2‘-脱氧鸟苷水平的研究 120例乙肝双阳性患者的干预研究 病毒表面抗原和黄曲霉毒素-白蛋白加合物，以及(2)测定 绿茶多酚对致癌物排泄的调节作用 收集尿样中的解毒产品黄曲霉毒素Bl-硫代尿酸 从研究参与者那里。这项拟议研究的结果将有助于 了解茶多酚的抗氧化作用机制 乙肝病毒和丙型肝炎病毒对人肝癌发生的调控作用 黄曲霉毒素。

DESCRIPTION (provided by applicant) The primary objective of this research project is to study the modulating effects of green tea polyphenols on reducing hepatocarcinogen-induced oxidative damages in high-risk human populations. Oxidative damage induced by reactive oxygen species in vivo plays important roles in human hepatocarcinogenesis primarily caused by chronic infection of hepatitis B/C viruses and exposure to dietary aflatoxins. The level of 8-hydroxy-2'- deoxyguanosine, a biomarker for oxidative DNA damage, increases in hepatitis B virus surface antigen positive and aflatoxin-exposed humans and in aflatoxin- treated animals. Dietary antioxidants are important components of cancer modulating agents, which have been proven to effectively target carcinogen biomarkers, including oxidative damages, in high-risk human populations. Among various identified dietary associated antioxidants, green tea and its polyphenols have been shown to be safe and highly effective in inhibition of a variety of carcinogen-induced oxidative damages, mutagenesis, and tumorigenesis in in vitro bioassays and in vivo animal models. The general hypothesis underlying this proposal is that green tea polyphenols have a protective effect against oxidative stress or damage induced by aflatoxin and hepatitis B/C viruses through the mechanisms of modulating aflatoxin metabolism and oxidated DNA damage. The specific aims include: (1) to determine antioxidative role of green tea polyphenols in inhibition of the level of 8-hydroxy-2'-deoxyguanosine in urine samples collected from an intervention study of 120 participants who are double positive for hepatitis B virus surface antigen and aflatoxin-albumin adducts, and (2) to determine the modulating effect of green tea polyphenols on excretion of carcinogen detoxifying product, aflatoxin Bl-mercapturic acid in urine samples collected from the study participants. The results of this proposed study will help to understand the mechanisms of antioxidative role of tea polyphenols in modulating human hepatocarcinogenesis caused by hepatitis B/C viruses and aflatoxins.