Overview of tumor promotion in animals
Overview of tumor promotion in animals
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动物肿瘤促进概述
DOI：
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发表时间：
1983
影响因子：
10.4
通讯作者：
T. Slaga
中科院分区：
文献类型：
--
作者：
T. Slaga
我们目前对两阶段致癌作用的理解涵盖了近四十年的研究。Berenblum首先提供了化学促进或共致癌作用的证据，他报告说，将巴豆油（弱致癌性或非致癌性）与小剂量苯并（a）芘（BP）交替应用于小鼠皮肤会诱导更多的肿瘤比单独使用BP。随后，Moltram发现，一个单一的亚致癌剂量的BP，然后多次应用巴豆油可以诱导大量的皮肤肿瘤。这些研究以及其他一些研究，例如Boutwell、Van Duuren和Hecker，负责定义两阶段致癌作用的启动和促进的许多重要方面。货车Duuren和Hecker。在小鼠皮肤中的起始阶段只需要一次直接作用致癌物或前致癌物的应用，并且基本上是一个不可逆的步骤，数据表明可能涉及体细胞突变。小鼠皮肤中的促进阶段可以通过各种弱或非致癌剂来完成，并且最初是可逆的，后来变得不可逆。目前的信息表明，皮肤肿瘤促进剂不是诱变性的，但会引起许多重要的表观遗传变化，如表皮增生，多胺，黑素和深色基底角质形成细胞以及其他胚胎条件的增加。最近，小鼠皮肤中的肿瘤促进被证明由至少两个阶段组成，其中每个阶段可以通过已知的启动子或弱或非促进剂来完成。促进的第一阶段的一些重要特征是：（1）仅需要第一阶段促进剂如佛波醇酯肿瘤促进剂、钙离子载体A23187、过氧化氢和创伤的一次应用;（2）作用是部分不可逆的;（3）深色基底角质形成细胞和胡萝卜素的增加是重要的;和（4）这种增加可以被类固醇和蛋白酶抑制剂抑制。第二阶段的促进最初是可逆的，但后来变得不可逆。多胺和表皮细胞增殖是促进第二阶段的重要事件。许多弱的或非促进剂，如美泽瑞因，是有效的第二阶段促进剂，可被视黄酸、类固醇和多胺合成抑制剂抵消。虽然皮肤肿瘤促进已经在小鼠中进行了广泛的研究，但并不是所有的小鼠品系和种群都对佛波酯肿瘤促进剂敏感。在这方面，C57 BL/6小鼠似乎对佛波酯肿瘤促进剂具有相当的抗性。此外，并非所有物种都同样容易受到佛波酯肿瘤促进。近年来，在许多实验性致癌系统中，如肝、膀胱、肺、结肠、食管、胃、乳腺、胰腺和培养细胞中，均显示出两阶段系统诱发肿瘤的普遍性。在这些系统中，各种各样的促进剂，如饮食，胆汁酸，激素，糖精，色氨酸，苯巴比妥，多氯联苯，多溴联苯和丁基羟基甲苯已被用于完成肿瘤促进阶段。目前尚不清楚其他实验致癌系统和人类癌症的诱导是否涉及与小鼠皮肤相似的一系列阶段。
Our present understanding of two-stage carcinogenesis encompasses almost four decades of research. Evidence for chemical promotion or cocarcinogenesis was first provided by Berenblum, who reported that a regimen of croton oil (weak or noncarcinogenic) applied alternately with small doses of benzo(a)pyrene (BP) to mouse skin induced a larger number of tumors than BP alone. Subsequently, Moltram found that a single subcarcinogenic dose of BP followed by multiple applications of croton oil could induce a large number of skin tumors. These investigations as well as a number of others, such as Boutwell, Van Duuren and Hecker, were responsible in defining many important aspects of the initiation and promotion of two-stage carcinogenesis. The initiation stage in mouse skin requires only a single application of either a direct-acting carcinogen or a procarcinogen and is essentially an irreversible step which as data suggests probably involves a somatic cell mutation. The promotion stage in mouse skin can be accomplished by a wide variety of weak or noncarcinogenic agents and is initially reversible later becoming irreversible. Current information suggests that skin tumor promoters are not mutagenic but bring about a number of important epigenetic changes, such as epidermal hyperplasia, and an increase in polyamines, prostaglandins and dark basal keratinocytes as well as other embryonic conditions. Recently, tumor promotion in mouse skin was shown to consist of at least two stages, in which each stage can be accomplished by either a known promoter or a weak or nonpromoting agent. Some of the important characteristics of the first stage of promotion are: (1) only one application of a first-stage promoter, such as phorbol ester tumor promoters, calcium ionophore A23187, hydrogen peroxide and wounding is needed; (2) the action is partially irreversible; (3) an increase in dark basal keratinocytes and prostaglandins is important; and (4) such an increase can be inhibited by antiinflammatory steroids and protease inhibitors. The second stage of promotion is initially reversible but later becomes irreversible. Polyamines and epidermal cell proliferation are important events in the second stage of promotion. A number of weak or nonpromoting agents, such as mezerein, are effective second-stage promoters which can be counteracted by retinoic acid, antiinflammatory steroids and polyamine synthesis inhibitors. Although skin tumor promotion has been extensively studied in mice, not all strains and stocks of mice are susceptible to phorbol ester tumor promoters. In this regard, the C57BL/6 mice appear to be fairly resistant to phorbol ester tumor promoters. In addition, not all species are equally susceptible to phorbol ester tumor promotion. Recently the generality of the two-stage system of inducing tumors has been shown to exist in a number of experimental carcinogenesis systems, such as the liver, bladder, lung, colon, esophagus, stomach, mammary gland, pancreas and cells in culture. In these systems, a wide variety of promoting agents such as diet, bile acids, hormones, saccharin, tryptophan, phenobarbital, polychlorinated biphenyls, polybrominated biphenyls and butylated hydroxytoluene have been used to accomplish the tumor promotion stage. It is not presently known if other experimental carcinogenesis systems and the induction of human cancer involves a series of stages similar to that in the mouse skin.
影响因子：
4.7
作者：
N. Scribner;J. Scribner
通讯作者：
N. Scribner;J. Scribner
影响因子：
56.9
作者：
SLAGA, TJ;KLEINSZANTO, AJP;TROSKO, JE
通讯作者：
TROSKO, JE