Tumor promoters and cell transformation.
Tumor promoters and cell transformation.
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DOI：
10.1016/0163-7258(84)90052-4
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发表时间：
1984
影响因子：
13.5
通讯作者：
Leila Diamond
中科院分区：
文献类型：
--
作者：
Leila Diamond
过去十年左右出现的大量流行病学和实验证据强化了癌症是多阶段、多因素过程的最终结果的概念。涉及的因素可能是自然界中的化学、物理或生物因素，其来源可能是内源或外源。因此，正如希金森(1983)所讨论的那样，人们可以认为，在人类中，一个人的整个生活方式在肿瘤疾病的演变中起着一定的作用。也许人类癌症多阶段、多因素性质的最好例子是石棉和吸烟在肺癌病因中的相互作用，与不吸烟、不吸烟的工人相比，综合因素使风险增加了近900倍(Selikoff和Hammond，1975)。病毒学家佩顿·罗斯是最早提出质疑的人之一，他质疑“致癌物质除了引起肿瘤变化外，是否还有其他作用”。他问一些人是否可能通过两种方式起作用：第一，将正常细胞转变为肿瘤细胞，第二，促进后者的增殖。在1944年的一份出版物中，首次在肿瘤发展的背景下使用了启动和促进这两个术语，Friedewald和Rous对癌症发生中涉及的单独和不同的影响进行了极好的分析和讨论。他们证明，通过一次治疗在兔皮肤中启动的潜伏肿瘤细胞，可以通过随后使用本身不会引发肿瘤变化的药物来强迫或促进皮肤显露出来。随后，Mottram(1944)、Berenblum and Shubik(1947,1949)和Berenblum(1954)开发的小鼠皮肤两阶段致癌方案定义了术语“启动”和“促进”。在这个现在经典的模型系统中，将低剂量、亚致癌剂量的致癌物质(引发剂)应用于皮肤，然后频繁、重复地应用促进剂。最终会发展成乳头状瘤，如果继续进行启动子治疗，一些癌症就会发展。致癌物的引发作用是不可逆的，而促进剂的作用则不可逆。
The concept that cancer is the end result of a multistage, multifactorial process has been reinforced by a wealth of epidemiological and experimental evidence that has appeared in the last decade or so. The factors involved may be chemical, physical or biological in nature and their sources may be endogenous or exogenous. Thus, one can consider that in humans one's entire lifestyle plays a part in the evolution of neoplastic disease, as Higginson (1983) has discussed. Perhaps the best example of the multistage, multifactorial nature of cancer in humans is the interaction of asbestos and cigarette smoking in the etiology of lung cancer, with the combined factors increasing the risk almost 900-fold compared to that in nonsmoking, nonasbestos workers (Selikoff and Hammond, 1975). The virologist, Peyton Rous, was one of the first to question whether" carcinogenic agents act in other ways besides bringing on neoplastic changes". He asked whether some may act in two ways: first, changing normal cells into neoplastic cells and, second, encouragingthe multiplication of the latter. In a 1944 publication that was the first to use the terms initiation and promotion in the context of tumor development, Friedewald and Rous presented a superb analysis and discussion of the separate and different effects involved in carcinogenesis. They demonstrated that latent tumor cells initiated in rabbit skin by one treatment could be forced or promoted to reveal themselves by subsequent treatment of the skin with agents which did not themselves initiate neoplastic change. Subsequently, the terms' initiation'and'promotion'have been defined by the protocol for two-stage carcinogenesis in mouse skin developed by Mottram (1944), Berenblum and Shubik (1947, 1949), and Berenblum (1954). In this now classic model system, a low, subcarcinogenic dose of a carcinogen (the initiator) is applied to the skin and this is followed by frequent, repeated applications of a promoter. Eventually papillomas develop and, if the promoter treatment is continued, some carcinomas develop. The initiating action by the carcinogen is irreversible, whereas the effect of the promoter, which is not