Is somatic mutation the major mechanism of malignant transformation?
Is somatic mutation the major mechanism of malignant transformation?
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体细胞突变是恶性转化的主要机制吗？
DOI：
10.1093/jnci/64.5.995
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发表时间：
1980
期刊：
影响因子：
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通讯作者：
H. Rubin
中科院分区：
文献类型：
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作者：
H. Rubin
约翰·凯恩斯在《癌症：科学与社会》(1)一书中指出，对正常动物细胞恶性转化为癌细胞的解释在很大程度上受到时代科学潮流的影响，而当前流行的是分子遗传学。因此，毫不奇怪，越来越多的人接受体细胞突变是细胞向恶性状态转变的因果事件，凯恩斯本人也对这一观点给予了很大的信任。体细胞突变假说的支持者同意，一些关于癌细胞的观察很难用体细胞突变假说来解释(2)，并承认可能有其他途径达到同样的目的，但他们通常坚持认为，DNA损伤是化学致癌的主要事件。从公共政策的角度来看，这一假设现在已经成为一个关键问题，因为对癌变的体细胞突变理论的信念是越来越广泛地使用细菌突变测试作为筛选环境中潜在化学致癌物的基础。因此，有必要对这一理论进行批判性评价，从而对测试的有效性进行批判性评价。恶性肿瘤是由不同程度地脱离正常生长和代谢控制的细胞组成的。当正常细胞停止繁殖时，恶性肿瘤中的细胞不仅会继续繁殖，而且它们产生的器官或组织的特征功能也会丧失。无论肿瘤起源于一个细胞还是几个细胞，这种改变根据定义都是遗传性的，因为它在肿瘤的大多数细胞中是永久存在的。这并不一定意味着这种变化是不可逆转的，因为有证据表明，来自某些肿瘤的一些细胞可以稳定地恢复到正常行为。最能说明这一现象的例子是老鼠的畸胎瘤。在小鼠和组织培养中反复传代后，该肿瘤仍保持其形成肿瘤的能力。然而，当将这些细胞注射到正常囊胚中时，产生了马赛克小鼠，它具有从肿瘤细胞衍生的各种正常组织，而没有肿瘤(3)。畸胎癌可以被认为是一种特殊的肿瘤：它起源于异位发育的生殖细胞，这些生殖细胞在肿瘤中不断表现出产生各种表面上正常组织类型的能力
In his book "Cancer: Science and Society" (1), John Cairns points out that explanations for the malignant transformation of normal animal cells into cancer cells are very much influenced by the scientific fashions of the times and that the current fashion is molecular genetics. Not surprisingly, therefore, it has become increasingly popular to accept somatic mutation as the causal event in the transformation of cells to the malignant state, and, indeed, Cairns himself gives much credence to this view. Proponents of the somatic mutation hypothesis agree that some observations about cancer cells would be difficult to explain by the somatic mutation hypothesis (2) and grant that there are probably other routes to the same end, but they generally hold to the view that damage to DNA is the primary event in chemical carcinogenesis. This hypothesis has now become a critical issue from the public policy point of view because a belief in the somatic mutation theory of carcinogenesis underlies the increasingly widespread use of bacterial mutation tests as screens for potential chemical carcinogens in [}ur environment. It is, therefore, appropriate to make a critical appraisal of this theory and, thereby, the validity of the tests. A malignant tumor is composed of cells that have, to varying degrees, escaped the normal controls on growth and metabolism. Not only do the cells in malignant tumors keep multiplying when normal cells would have stopped, but also the integration of functions that characterize the organ or tissue from which they arose is lost. Whether the tumor originates in one or several cells, the alteration is by definition hereditary because it is perpetuated in most of the cells of the tumor. This :ioes not necessarily mean that the change is irreversible, inasmuch as evidence indicates that some cells from some tumors can be stably restored to normal behavior. The most dramatic illustration of this phenomenon is in the teratocarcinoma of mice. This tumor retains its capacity to form tumors upon repeated passages in mice and tissue culture. However, when the cells are injected into a normal blastula, a mosaic mouse is produced, which has various normal tissues derived from the tumor cells and no tumors (3). The teratocarcinoma may be considered an exceptional tumor: It arises from ectopically developing germ cells that constantly exhibit the capacity to produce a variety of apparently normal tissue types in the tumor