文章：

先天与后天——化学致癌的教训

Nature and nurture – lessons from chemical carcinogenesis

原文发布日期：2005-02-01

DOI: 10.1038/nrc1546

类型: Review Article

开放获取: 否

要点：

1. Associations between cancer and occupational exposures can be dated back into the sixteenth century.
2. Today, about 200 different chemical compounds and mixtures are known or anticipated to be human carcinogens.
3. The great majority of human chemical carcinogens require metabolic activation to elicit detrimental effects. The activity of 'xenobiotic metabolizing enzymes' such as cytochrome-P450-dependent monooxygenases, glutathione S-transferases, sulphotransferases and others are required for activation (toxication) of important carcinogens.
4. Human carcinogens act through a variety of genotoxic and non-genotoxic mechanisms. DNA binding and induction of mutations in cancer-susceptibility genes, such as TP53 and KRAS, are import mechanisms of tumour initiation. In addition, the accompanying ability of many compounds to promote the outgrowth of transformed cell clones has been acknowledged.
5. The preferential formation of certain stereoisomers during metabolic activation of genotoxic carcinogens can determine the level of DNA damage, the efficiency of DNA repair, and the carcinogenic potency of a compound.
6. Humans are exposed to mixtures of compounds with different degrees of biological activity. Analysis of compound-specific mutational patterns provides valuable clues on the contribution of individual chemicals (or single classes of chemicals) to the overall biological response to these mixtures observed in certain tissues.

要点翻译：

1. 癌症与职业暴露之间的关联可追溯至十六世纪。
2. 如今，已有约200种不同的化合物和混合物被确认或预计为人类致癌物。
3. 绝大多数人类化学致癌物需要经过代谢活化才能产生有害效应。诸如细胞色素P450依赖性单加氧酶、谷胱甘肽S-转移酶、磺基转移酶等"外源性代谢酶"的活性是重要致癌物活化（毒化）的必要条件。
4. 人类致癌物通过多种遗传毒性和非遗传毒性机制发挥作用。DNA结合以及对TP53、KRAS等癌症易感基因的诱变，是肿瘤启动的重要机制。此外，许多化合物还具有促进转化细胞克隆生长的能力。
5. 遗传毒性致癌物代谢活化过程中特定立体异构体的优先形成，可决定DNA损伤程度、DNA修复效率及化合物的致癌效力。
6. 人类暴露于具有不同生物活性的化合物混合物。通过分析化合物特异性突变模式，可为揭示特定组织中个体化学物（或单一类别化学物）对这些混合物总体生物反应的贡献提供重要线索。

英文摘要：

The roles of genetic constitution versus environmental factors in cancer development have been a matter of debate even long before the discovery of 'oncogenes'. Evidence from epidemiological, occupational and migration studies has consistently pointed to environmental factors as the major contributing factors to cancer, so it seems reasonable to discuss the importance of chemical carcinogenesis in the present 'age of cancer genetics'.

摘要翻译： 

在癌症发展过程中，遗传因素与环境因素的作用之争，早在‘癌基因’被发现之前就已存在。来自流行病学、职业病学及移民研究的证据一致表明，环境因素是癌症的主要诱因，因此，在当今‘癌症遗传学时代’探讨化学致癌的重要性显得尤为必要。

原文链接：

Nature and nurture – lessons from chemical carcinogenesis