Nervous-system-specific carcinogenesis by ethylnitrosourea in the rat: molecular and cellular aspects
Nervous-system-specific carcinogenesis by ethylnitrosourea in the rat: molecular and cellular aspects
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乙基亚硝基脲对大鼠神经系统特异性致癌作用：分子和细胞方面
DOI：
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发表时间：
1977
期刊：
影响因子：
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通讯作者：
L. Lomakina
中科院分区：
文献类型：
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作者：
M. Rajewsky;L. Augenlicht;H. Biessmann;R. Goth;D. Hülser;O. Laerum;L. Lomakina
目前的证据表明，肿瘤转化过程可以通过靶细胞遗传物质的直接结构改变来启动。相应地，几乎所有被测试的致癌物的致癌性和突变性之间都有很强的相关性(McCann et A1。1975年；孟德萨诺等人。1976年)。大量化学致癌物的亲电性、终极代谢衍生物与DNA的共价结合已被证明(Miller和Miller，1974)。此外，许多芳香族致癌物能够与DNA堆积相互作用(Ames等人)。1972年)。另一方面，对致癌剂的代谢激活(Magee 1974)及其与细胞成分的初级相互作用的物理化学的广泛研究迄今未能在分子水平上建立一种特定的、常见的“致癌”反应类型(Heidelberger 1975)。相反，似乎由不同类型的致癌剂引起的各种初始分子改变可能具有增加“肿瘤表型”表达的可能性的特性。然而，肿瘤转化的可能性不太可能是原发致癌物-细胞相互作用的类型和程度的简单函数。目标细胞在接触致癌物时的特定表型特性，即它们的分化和增殖状态，可能是同样重要的决定因素(Rajeski 1972；Goth和Rajesky 1974a，b；Rajcwsky et A1)。1976年)。在这方面特别相关的是靶细胞的增殖率，因为似乎需要重复几轮DNA复制和细胞分裂(或对致癌物质引起的基因组改变的“固定”(Sachs 1966；Rajeski 1967,1972；Kakunaga 1974)，
Present evidence suggests that the process of neoplastic transformation can be initiated by direct structural alterations of the genetic material of target cells. Correspondingly, there is a strong correlation between oncogenicity and mutagenicity for almost all carcinogens tested (McCann et a1. 1975; Montesano et ar. 1976). Covalent binding to DNA has been shown for the electrophilic, ultimate metabolic derivatives of a large number of chemical carcinogens (Miller and Miller 1974). Many aromatic carcinogens are, in addition, capable of stacking interactions with DNA (Ames et al. 1972). On the other hand, extensive studies on both the metabolic activation of oncogenic agents (Magee 1974) and the physical chemistry of their primary interactions with cellular constituents have thus far failed to establish a specific, common type of "oncogenic" reaction at the molecular level (Heidelberger 1975). Instead, it appears that a variety of initial molecular alterations caused by different types of carcinogenic agents may share the property of increasing the probability for expression of a "neoplastic phenotype." The probability of neoplastic transfonnation, however, is unlikely to be a simple function of the type and degree of primary carcinogen-cell interaction. Specific phenotypic properties of the target cells at the time of exposure to a carcinogen, i.e., their state of differentiation and proliferation, may be equally important determinants (Rajewsky 1972; Goth and Rajewsky 1974a,b; Rajcwsky et a1. 1976). Particularly relevant in this context are the rate of target-cell proliferation, since repeated rounds of DNA replication and cell division seem to be required (or the "fixation" of carcinogen-induced genome alterations (Sachs 1966; Rajewsky 1967, 1972; Kakunaga 1974),