Modulation of Oxidative Damage by Tea Polyphenols

描述（由申请人提供） 本研究的主要目的是研究 绿色茶多酚对肝癌诱导的抗肿瘤作用 高风险人群中的氧化损伤。 氧化损伤 活性氧在人体内起着重要的作用 B/C型肝炎慢性感染致肝癌 病毒和暴露于膳食黄曲霉毒素。 8-羟基-2 '- 脱氧鸟苷是氧化性DNA损伤的生物标志物，在B型肝炎中增加 病毒表面抗原阳性和黄曲霉毒素暴露的人和黄曲霉毒素- 对待动物。 膳食抗氧化剂是癌症的重要组成部分 调节剂，已被证明可有效靶向致癌物 生物标志物，包括氧化损伤，在高危人群中。 在各种确定的饮食相关抗氧化剂中，绿色茶及其 多酚已被证明是安全的，并且在抑制 各种致癌物诱导的氧化损伤、致突变和 在体外生物测定和体内动物模型中的肿瘤发生。 总 该建议的基础假设是绿色茶多酚具有 对黄曲霉毒素诱导的氧化应激或损伤的保护作用， 通过调节黄曲霉毒素机制的B/C型肝炎病毒 代谢和氧化DNA损伤。 具体目标包括：（1） 测定绿色茶多酚的抗氧化作用， 从一名儿童的尿液样本中检测到8-羟基-2 '-脱氧鸟苷的水平 120例B型肝炎双阳性者干预研究 病毒表面抗原和黄曲霉毒素-白蛋白加合物，以及（2）确定 绿色茶多酚对致癌物排泄的调节作用 尿液样本中黄曲霉毒素B1-巯基尿酸含量 从研究参与者。 这项研究的结果将有助于 了解茶多酚的抗氧化作用机制， 调节由B/C型肝炎病毒引起的人肝癌发生， 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.