Bellé Robert, Le Bouffant Ronan, Morales Julia, Cosson Bertrand, Cormier Patrick, Mulner-Lorillon Odile
Centre National de la Recherche Scientifique, UMR 7150 Mer & Santé, France.
J Soc Biol. 2007;201(3):317-27. doi: 10.1051/jbio:2007030.
Cell division is an essential process for heredity, maintenance and evolution of the whole living kingdom. Sea urchin early development represents an excellent experimental model for the analysis of cell cycle checkpoint mechanisms since embryonic cells contain a functional DNA-damage checkpoint and since the whole sea urchin genome is sequenced. The DNA-damaged checkpoint is responsible for an arrest in the cell cycle when DNA is damaged or incorrectly replicated, for activation of the DNA repair mechanism, and for commitment to cell death by apoptosis in the case of failure to repair. New insights in cancer biology lead to two fundamental concepts about the very first origin of cancerogenesis. Cancers result from dysfunction of DNA-damaged checkpoints and cancers appear as a result of normal stem cell (NCS) transformation into a cancer stem cell (CSC). The second aspect suggests a new definition of "cancer", since CSC can be detected well before any clinical evidence. Since early development starts from the zygote, which is a primary stem cell, sea urchin early development allows analysis of the early steps of the cancerization process. Although sea urchins do not develop cancers, the model is alternative and complementary to stem cells which are not easy to isolate, do not divide in a short time and do not divide synchronously. In the field of toxicology and incidence on human health, the sea urchin experimental model allows assessment of cancer risk from single or combined molecules long before any epidemiologic evidence is available. Sea urchin embryos were used to test the worldwide used pesticide Roundup that contains glyphosate as the active herbicide agent; it was shown to activate the DNA-damage checkpoint of the first cell cycle of development. The model therefore allows considerable increase in risk evaluation of new products in the field of cancer and offers a tool for the discovery of molecular markers for early diagnostic in cancer biology. Prevention and early diagnosis are two decisive elements of human cancer therapy.
细胞分裂是整个生物界遗传、维持和进化的基本过程。海胆早期发育是分析细胞周期检查点机制的绝佳实验模型，因为胚胎细胞含有功能性DNA损伤检查点，且海胆全基因组已测序。DNA损伤检查点负责在DNA受损或复制错误时使细胞周期停滞，激活DNA修复机制，并在修复失败时促使细胞通过凋亡死亡。癌症生物学的新见解产生了关于癌症发生最初起源的两个基本概念。癌症源于DNA损伤检查点功能失调，并且癌症是正常干细胞（NCS）转化为癌症干细胞（CSC）的结果。第二个方面提出了“癌症”的新定义，因为在任何临床证据出现之前就能很好地检测到CSC。由于早期发育从受精卵开始，而受精卵是一种原始干细胞，海胆早期发育有助于分析癌变过程的早期步骤。虽然海胆不会患癌症，但该模型是对干细胞模型的补充和替代，干细胞不易分离，短时间内不分裂且不同步分裂。在毒理学领域以及对人类健康的影响方面，海胆实验模型能够在任何流行病学证据出现之前很久，就评估单一或组合分子的癌症风险。海胆胚胎被用于测试全球使用的含有草甘膦作为活性除草剂成分的农药农达；结果表明其能激活发育第一个细胞周期的DNA损伤检查点。因此，该模型可大幅提高癌症领域新产品的风险评估，并为发现癌症生物学早期诊断的分子标志物提供工具。预防和早期诊断是人类癌症治疗的两个决定性因素。
