Cerutti P A
Department of Carcinogenesis, Swiss Institute for Experimental Cancer Research, Epalinges/Lausanne.
Environ Health Perspect. 1989 May;81:39-43. doi: 10.1289/ehp.898139.
A major goal in multistep carcinogenesis research is the integration of recent findings obtained by sophisticated molecular-genetic and cytogenetic analysis of cancer into the more descriptive concepts of experimental pathology. It is proposed that the creation of a promotable cell in carcinogenic initiation requires a response modification to extracellular or intercellular signals. Different types of response modification can be distinguished: changes in the receptors for growth and differentiation factors and their cytoplasmic and nuclear signal transduction pathways; increased resistance of initiated cells to cytotoxic agents; alterations in junctional cell-to-cell communications. The challenge of a response-modified cell to an appropriate promoter results in its selection and clonal expansion, usually to a benign tumor. In addition, for malignancy, chromosomal changes are required that affect cellular functions that can play a role early or late in tumorigenesis. These concepts are illustrated with examples from oncogene research and oxidant promotion.
多步骤致癌作用研究的一个主要目标是，将通过对癌症进行精密分子遗传学和细胞遗传学分析所获得的最新发现，整合到实验病理学更具描述性的概念中。有人提出，在致癌起始过程中产生一个可被促进的细胞需要对细胞外或细胞间信号的反应进行修饰。可以区分出不同类型的反应修饰：生长和分化因子的受体及其细胞质和核信号转导途径的变化；起始细胞对细胞毒性剂的抗性增加；细胞间连接通讯的改变。一个反应修饰后的细胞对合适的促进剂产生的反应会导致其被选择并克隆扩增，通常形成良性肿瘤。此外，对于恶性肿瘤而言，需要发生染色体变化，这些变化会影响在肿瘤发生早期或晚期可能起作用的细胞功能。这些概念通过癌基因研究和氧化剂促进作用的例子进行说明。
