Epidemiological studies provide convincing evidence for an inverse relation between quantities of fruit and vegetables consumed and the risk of developing cancer. A major mechanism for protection involves induction of phase 2 detoxication enzymes that promote elimination of carcinogens and boost antioxidant capacity. Many edible plants, most notably 3-day-old broccoli sprouts, contain potent phase 2 enzyme inducer activity in the form of isothiocyanates or their glucosinolate precursors. In animals, sulforaphane, derived from the principal glucosinolate (glucoraphanin) of broccoli sprouts, is a very potent inducer of phase 2 enzyme activity and protects against chemical carcinogenesis. The objective of this study is to translate and evaluate these laboratory findings in a high-risk human population. Previous trials have afforded important information on the safety, metabolism and urinary disposition of isothiocyanates, and on the activation of glucosinolates. Since it is possible to grow broccoli sprouts with a consistent composition of glucoraphanin, we propose to conduct a clinical trial to provide the first assessment of the efficacy of broccoli sprouts to modulate the metabolism of an environmental carcinogen in humans. The target population for this clinical trial is residents of Qidong, People's Republic of China, who are at high risk for development of hepatocellular carcinoma, in part from consumption of dietary staples contaminated with aflatoxins. The capacity of ingestion of broccoli sprouts to reduce the urinary excretion of aflatoxin-DNA damage products will provide the primary means for measuring efficacy of the intervention. This clinical trial will provide a rigorous assessment of the usefulness of modulating expression of carcinogen detoxication enzymes by means of a food containing a standardized level of a phytochemical as a general strategy for chemoprevention in humans.
| Kensler, Thomas W; Chen, Jian-Guo; Egner, Patricia A et al. (2005) Effects of glucosinolate-rich broccoli sprouts on urinary levels of aflatoxin-DNA adducts and phenanthrene tetraols in a randomized clinical trial in He Zuo township, Qidong, People's Republic of China. Cancer Epidemiol Biomarkers Prev 14:2605-13 |
| Kensler, Thomas W; Egner, Patricia A; Wang, Jin-Bing et al. (2004) Chemoprevention of hepatocellular carcinoma in aflatoxin endemic areas. Gastroenterology 127:S310-8 |
