Bowen P E, Mobarhan S
Department of Human Nutrition and Dietetics, University of Illinois at Chicago 60612, USA.
Am J Clin Nutr. 1995 Dec;62(6 Suppl):1403S-1409S. doi: 10.1093/ajcn/62.6.1403S.
Evidence from intervention trials with vitamins E and C and beta-carotene are reviewed as well as evidence from trials that have used intermediate endpoints with a special emphasis on biomarkers of cancer of the colorectum. The methodologic issues that require resolution before a second generation of clinical trials are launched to assess the efficacy of these antioxidants in the prevention of cancer are identified. Specific concerns regarding the validation of pathologic biomarkers of cancer and biochemical markers of mechanism of action for the antioxidants are discussed. Cellular proliferation indexes in the colon are used as an example of pathologic biomarkers for cancer and the measurement of plasma and tissue malondialdehyde concentrations is used as an example of problems with the development of biochemical markers of oxidative stress that can be used in prevention trials. The use of DNA oxidation products as promising biomarkers is also discussed.
对维生素E、维生素C和β-胡萝卜素干预试验的证据以及使用中间终点的试验证据进行了综述,特别强调了结直肠癌的生物标志物。确定了在开展第二代临床试验以评估这些抗氧化剂预防癌症的疗效之前需要解决的方法学问题。讨论了关于癌症病理生物标志物的验证以及抗氧化剂作用机制的生化标志物的具体问题。以结肠中的细胞增殖指数作为癌症病理生物标志物的示例,并以血浆和组织丙二醛浓度的测量作为可用于预防试验的氧化应激生化标志物开发问题的示例。还讨论了使用DNA氧化产物作为有前景的生物标志物的情况。