Fenton Jenifer I, Hord Norman G
Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892-7361, USA.
Carcinogenesis. 2006 May;27(5):893-902. doi: 10.1093/carcin/bgi355. Epub 2006 Feb 10.
Clinical evidence reveals that the efficacy of dietary factors to prevent cancer is probably stage-dependent. The ability to demonstrate stage-specific effects of dietary compounds on normal, preneoplastic and malignant cell models may provide insights into puzzling clinical results from cancer chemoprevention trials. The relevance of these models to the field of cancer prevention is immense and will undoubtedly facilitate the ability to discover which dietary factors are most effective at preventing cancer and which, if any, specific steps in neoplastic transformation render cells refractory to the effects of dietary compounds. There are illustrative examples where exposure of high-risk individuals to dietary chemopreventive agents increases rather than decreases cancer risk. While geneticists and clinical oncologists acknowledge the morphological continuum along which tumors develop in specific tissues, tumor cells, rather than normal and preneoplastic cells, continue to be the primary in vitro reductionist tool employed to elucidate mechanisms underlying disease progression and to investigate the potential utility of dietary as well as other chemopreventive agents. Currently, there are few relevant model systems to study the progression of neoplastic transformation, especially in epithelial cells. We highlight examples of model systems isolated from prostate, breast, endometrial and intestinal tissue, with special emphasis on a specific set of non-tumorigenic, conditionally immortal cell lines derived from C57/BL6 mice [YAMC (Young Adult Mouse Colon cells; Apc+/+) cells and IMCE (Immorto-Min Colonic Epithelium cells; ApcMin/+) cells] that have yielded important information on early events in colorectal neoplasia development. These cell lines are an illustrative example of how researchers can examine stage-dependent effects of specific dietary components on carcinogenesis. The utilization of cell culture systems modeling early, middle and late stages of tumorigenesis will yield important insights into mechanisms by which dietary components impact cancer progression.
临床证据表明，饮食因素预防癌症的功效可能具有阶段依赖性。证明饮食化合物对正常、癌前和恶性细胞模型具有阶段特异性作用的能力，可能有助于解释癌症化学预防试验中令人困惑的临床结果。这些模型与癌症预防领域的相关性极大，无疑将有助于发现哪些饮食因素在预防癌症方面最有效，以及在肿瘤转化过程中，哪些特定步骤（如果有的话）会使细胞对饮食化合物的作用产生抗性。有一些实例表明，高危个体接触饮食化学预防剂后，癌症风险非但没有降低，反而增加了。虽然遗传学家和临床肿瘤学家承认肿瘤在特定组织中发展的形态学连续性，但肿瘤细胞而非正常细胞和癌前细胞，仍然是用于阐明疾病进展机制以及研究饮食及其他化学预防剂潜在效用的主要体外简化工具。目前，用于研究肿瘤转化过程，尤其是上皮细胞肿瘤转化过程的相关模型系统很少。我们重点介绍了从前列腺、乳腺、子宫内膜和肠道组织中分离出的模型系统实例，特别强调了一组源自C57/BL6小鼠的特定非致瘤性、条件性永生化细胞系[YAMC（年轻成年小鼠结肠细胞；Apc+/+细胞）和IMCE（永生化小型结肠上皮细胞；ApcMin/+细胞）]，这些细胞系已经提供了有关结直肠癌发生早期事件的重要信息。这些细胞系是研究人员如何研究特定饮食成分对致癌作用的阶段依赖性影响的一个典型例子。利用模拟肿瘤发生早期、中期和晚期阶段的细胞培养系统，将有助于深入了解饮食成分影响癌症进展的机制。
