DNA Damage: Fruit & Vegetable Effects in a Feeding Trial

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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.