DNA Damage: Fruit & Vegetable Effects in a Feeding Trial

描述（由申请人提供）： 流行病学研究表明，增加水果和蔬菜的消费可以降低不同部位的癌症风险。许多植物化学物质在体外和动物研究中都显示出通过几种机制预防癌症。某些植物化学物质的抗氧化能力是一种潜在的机制，通过这种机制，富含水果和蔬菜的饮食可以降低癌症风险。DNA损伤导致的累积突变导致癌症的发展。抗氧化剂可以减少细胞DNA损伤，从而降低突变率。另一个潜在的机制是通过几类植物化学物质改变I相和II相生物转化酶活性的能力，从而调节致癌物质的代谢。解毒过程在防御化学诱导的致癌作用中起着至关重要的作用;它中断或阻止致癌物质形成DNA加合物。DNA损伤已被确定为评估癌症易感性的相关替代生物标志物，碱性单细胞凝胶电泳（彗星试验）已成为评估DNA损伤的标准方法之一。 本研究的主要目的是确定，在我们现有的对照，随机，交叉喂养试验，是否定义的饮食干预10份/天的水果和蔬菜（十字花科蔬菜，大豆食品，柑橘类水果）2周影响人类淋巴细胞DNA损伤和抵抗H2 O2诱导的损伤测量彗星试验。我们假设，与不含水果和蔬菜的基础饮食相比，高水果和蔬菜饮食将：（a）减少内源性淋巴细胞DNA链断裂;和（B）增加淋巴细胞对H2 O2诱导的DNA损伤的抗性。我们也将探讨UGT和GST多态性对DNA损伤的影响，并研究内源性抗氧化剂胆红素血清浓度与淋巴细胞DNA损伤之间的关系。现有的干预措施提供了一个理想的设计，以评估生物转化酶系统和人类DNA损伤之间的关系。

DESCRIPTION (provided by applicant): Epidemiologic studies suggest that increased fruit and vegetable consumption reduce cancer risk at various sites. Numerous phytochemicals have been shown in both in vitro and animal studies to be cancer preventive through several mechanisms. The antioxidant capacity of certain phytochemicals is one potential mechanism by which diets high in fruit and vegetables may reduce cancer risk. Cumulative mutations resulting from DNA damage lead to the development of cancer. Antioxidants can reduce cellular DNA damage, and hence reduce mutation rate. Another potential mechanism is through the ability of several classes of phytochemicals to alter phase I and II biotransformation enzyme activities, and thereby modulate carcinogen metabolism. The detoxification process plays a critical role in the defense against chemically-induced carcinogenesis; it interrupts or prevents the carcinogens from forming DNA adducts. DNA damage has been identified as a relevant surrogate biomarker for assessing cancer susceptibility, and alkaline single cell gel electrophoresis (Comet assay) has become one of the standard methods for assessing DNA damage. The primary aim of this study is to determine, in our existing controlled, randomized, cross-over feeding trial, whether a defined dietary intervention of 10 servings/d of fruit and vegetables (cruciferous vegetables, soy foods, and citrus fruits) for 2 weeks affects human lymphocyte DNA damage and resistance to H202-induced damage measured by the Comet assay. We hypothesize that, compared to a fruit and vegetable-free basal diet, the high fruit and vegetable diet will: (a) decrease endogenous lymphocyte DNA strand breaks; and (b) increase lymphocyte resistance to H202-induced DNA damage. We will also explore the effect of UGT and GST polymorphisms on DNA damage and examine the relationship between serum concentrations of the endogenous antioxidant bilirubin and lymphocyte DNA damage. The existing intervention provides an ideal design in which to evaluate the relationships between biotransformation enzyme systems and DNA damage in humans.