常见化学品或可共同行动来增加个体癌症风险

  刊登在国际杂志Carcinogenesis上的一篇研究论文中，来自俄勒冈州立大学等处的研究人员通过研究表示，常常被认为低剂量水平下安全的常见环境化学品单独或在一起作用时会干扰人类的组织功能，最终引发癌症。在进行长达3年的关于环境影响致癌的研究中，科学家们分析研究了常见的85种化学品在低剂量下同人类致癌之间的关系。
  文章中研究者回顾了一些化学品的作用，这些化学品可以帮助抵御一系列对癌症发生重要的机制，利用多个实验室研究、大型的癌症数据库以及模型来预测癌症的发展，研究者对比了化学品生物活性的模式和已知的11中癌症标志之间的关联，癌症标志即是一些和早期肿瘤发生相关的细胞模式及遗传破坏等。
  常见的化学品，比如双酚A（BPA），其通常用于成型的食物或饮料容器；鱼藤酮，一种广谱的杀虫剂；百草枯，一种农业除草剂；三氯生，一种用于肥皂和化妆品的杀菌剂。研究者表示，85种化学品中的50种都被认为可以以多种途径来干扰细胞的功能，而这和癌症早期发生直接相关。研究者发现其中有13种化学品存在剂量响应阈值，即当其达到一定水平时就被认为是有毒的。
  研究者William Bisson说道，我们研究发现这些化学品可以协同作用来增加个体患癌风险，比如，EDTA，一种用于制造业和医学领域的金属离子结合化合物就会干扰机体损伤基因的修复，EDTA并不会引发机体遗传突变，但如果当你暴露于EDTA同诱变剂共同存在的情况下，这就会增加机体患癌效应，因为EDTA会干扰DNA的修复。
  本文研究的主要目的就是研究环境影响机体患癌风险的原因和机制，研究者希望通过更多深入的研究来评估多种化学品的暴露对于机体患癌的影响。传统的风险评估仅仅只关注于寻找单一的化学品及其单一作用，这种方法或许会低估癌症的风险，而本文研究中研究者则采用了不同的策略，检测了随时间进程往后，由低剂量化学品暴露引发的机体的变化。
  癌症是一种恶性疾病，其发生往往会经历多种模式阶段，很多时候癌症会有一定的潜伏期，而研究者必须有效抓住某一个角度来研究癌症不同模式的复杂性及其发病机理；更好地理解常见化学品致癌的过程和原因对于后期开发有效的疗法来预防、检测及治疗癌症或将带来巨大帮助。（转化医学网360zhyx.com）
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转化医学网推荐的原文摘要：

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead
Carcinogenesis     doi: 10.1093/carcin/bgv039
William H. Goodson III*, Leroy Lowe1,2, David O. Carpenter3, Michael Gilbertson4, Abdul Manaf Ali5 et al
Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.