Increased cell division as a cause of human cancer.
Increased cell division as a cause of human cancer.
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发表时间：
1990-12
期刊：
影响因子：
11.2
通讯作者：
S. Preston‐Martin;M. Pike;R. Ross;P. A. Jones;B. Henderson
中科院分区：
文献类型：
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作者：
S. Preston‐Martin;M. Pike;R. Ross;P. A. Jones;B. Henderson
致癌作用的研究越来越多地集中在没有遗传毒性的化学品上，但在高剂量下，显然可以通过增加细胞增殖诱发癌症。我们推测，由外部或内部因素刺激的细胞分裂本身的增加也与许多人类癌症的发展有关。虽然这一假设在实验文献中得到了充分的证实，但它尚未被推广为人类致癌的重要机制。在这种增加的细胞分裂模型下，癌症的发病机理可能是由于细胞分裂过程中诱导的分子遗传错误以及恶性或癌前细胞的生长控制改变。人类癌症的分子遗传学分析表明，肿瘤细胞含有多种遗传缺陷，包括癌基因的突变、易位和扩增，并且对于推定的肿瘤抑制基因被还原为纯合性;这些现象都需要细胞分裂才能发生和固定。细胞分裂增加会增加发生此类事件的风险。这种遗传错误的组合的积累导致肿瘤表型。讨论了人类癌症的例子，其中增加的细胞分裂，这驱动了遗传错误的积累，并可能导致肿瘤转化，是由激素，药物，感染剂，化学品，物理或机械创伤，和其他慢性刺激引起的。
Carcinogenesis research is increasingly focused on chemicals that are not genotoxic and yet, at high doses, can induce cancer, apparently by increasing cell proliferation. We hypothesize that increased cell division per se stimulated by external or internal factors is also associated with the development of many human cancers. Although this hypothesis is well substantiated in the experimental literature, it has not been generalized as an important mechanism for carcinogenesis in human populations. Under this increased cell division model, the pathogenesis of cancer may result from molecular genetic errors induced during the process of cell division and from altered growth control of malignant or premalignant cells. Molecular genetic analysis of human cancers has shown that tumor cells contain multiple genetic defects including mutations, translocations, and amplifications of oncogenes and are reduced to homozygosity for putative tumor suppressor genes; these phenomena all require cell division for their occurrence and fixation. Increased cell division increases the risk of such events occurring. An accumulation of a combination of such genetic errors leads to a neoplastic phenotype. Examples are discussed of human cancers in which increased cell division, which drives the accumulation of genetic errors and can lead to neoplastic transformation, is caused by hormones, drugs, infectious agents, chemicals, physical or mechanical trauma, and other chronic irritation.