Carcinogenesis: a fifty-year historical perspective.
Carcinogenesis: a fifty-year historical perspective.
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致癌作用：五十年的历史视角。
DOI：
10.1111/1523-1747.ep13075095
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Lowy,DR
中科院分区：
文献类型：
--
作者：
Bickers,DR;Lowy,DR
在过去的50年里，我们对皮肤癌发生的了解取得了巨大的进步。紫外光、化学致癌物和肿瘤病毒诱导的致癌模型系统已经被开发和研究。这些结果强调了诱导剂、宿主因素和其他环境因素之间相互作用在确定发生恶性肿瘤的可能性方面的重要性。对着色性干皮病的研究表明，无法修复紫外光引起的DNA损伤可以显著加速紫外光的致癌作用。化学致癌物诱发小鼠皮肤鳞状细胞癌代表了一个系统，在这个系统中，我们对致癌的一般理解做出了特别重要的概念性贡献。这类研究是第一批表明细胞在向恶性转化的过程中经历了不同阶段的研究之一，这意味着可能需要几个离散的变化来将细胞从正常转化为恶性。这些观察为理解在许多形式的临床癌症中看到的长潜伏期提供了一个实验框架，在这些癌症中，诱导剂通常仍然未知。乳头瘤病毒是皮肤良性肿瘤的重要致病因子，近年来发现其与多种上皮性恶性肿瘤，特别是某些生殖器肿瘤有关，近年来，致癌研究的重点已转向机制分析和特定基因在肿瘤发生中的作用。这些分析表明，在细胞中发生了几个可识别的基因改变后，在分子水平上发生了皮肤癌的发生。因此，早期研究提供了癌症是一个多步骤过程的强有力证据的皮肤癌发生的模型系统，现在正在识别其变化有助于恶性转化的特定基因。这篇以历史为导向的综述强调了皮肤癌发生的这些和相关的进展，并提出了一些可能在未来的研究中解决的问题。
The past 50 years have witnessed enormous progress in our understanding of cutaneous carcinogenesis. Model systems of carcinogenesis induced by ultraviolet light, chemical carcinogens, and tumor viruses have been developed and studied. The results emphasize the importance of the interplay between the inducing agent, host factors, and other environmental factors in determining the likelihood of developing malignant tumors. The study of xeroderma pigmentosum has indicated how the inability to repair ultraviolet light induced DNA damage can markedly accelerate the carinogenic effects of UV light. The induction of cutaneous squamous cell carcinomas in mice by chemical carcinogens has represented a system in which especially important conceptual contributions have been made to our understanding of carcinogenesis in general. Such studies were among the first to indicate that cells pass through various stages in the progression to malignancy, which implies that several discrete changes may be required to convert cells from normal to malignant. These observations have provided an experimental framework in which to understand the long latency periods seen in many forms of clinical cancer, where the inducing agents usually remain unknown. Papillomaviruses represent important agents of benign cutaneous tumors which have recently been implicated in a variety of epithelial malignancies, especially certain genital neoplasms.In recent years, the focus of carcinogenesis studies has shifted to mechanistic analyses and to the contribution of specific genes to tumorigenesis. These analyses have suggested that cutaneous carinogenesis at the molecular level results after several identifiable genetic alterations have occurred in the cell. Thus model systems of cutaneous carcinogenesis, in which early studies provided strong evidence for cancer being a multistep process, are now identifying the specific genes whose alterations contribute to malignant conversion. This historically oriented review highlights these and related advances in understanding cutaneous carcinogenesis and suggests some questions that may be addressed in future studies.