Strauss Harlee S, Heiger-Bernays Wendy
H. Strauss Associates, Inc., Natick, Massachusetts 01760, USA.
Toxicol Pathol. 2012 Oct;40(7):995-1003. doi: 10.1177/0192623312443320. Epub 2012 May 2.
Epidemiological studies increasingly indicate that polychlorinated biphenyls (PCBs) contribute to the risk of non-Hodgkin's lymphoma (NHL). In rodent bioassays, PCBs have long been demonstrated to be liver carcinogens, and excess tumors in the thyroid, lung, and other organs have been observed in more recent studies. Leukemias and lymphomas now classified as NHL were observed in one bioassay in which a concurrent infection was also reported. Clinical and epidemiological studies show immunosuppression and inflammation are strong risk factors for NHL, and both epidemiology and toxicology studies show that PCBs are immunosuppressive and cause inflammation. We reviewed published carcinogenesis bioassays conducted using commercial PCB products, individual congeners, and congener mixtures, with a focus on bioassay protocols and immune-related observations. Based on a mode-of-action framework for PCBs, we suggest that an immune challenge in conjunction with PCB exposure may be necessary for the observation of NHL. We conclude that the lack of concordance between human epidemiology and animal bioassays with respect to NHL may simply be the result of the bioassay methodology used, and not a difference in underlying biology. The lack of concordance should not be construed as evidence that PCBs do not contribute to the risk of NHL.
流行病学研究越来越表明，多氯联苯（PCBs）会增加非霍奇金淋巴瘤（NHL）的发病风险。在啮齿动物生物测定中，长期以来已证实多氯联苯是肝脏致癌物，并且在最近的研究中还观察到甲状腺、肺和其他器官出现过多肿瘤。在一项生物测定中观察到了现在归类为非霍奇金淋巴瘤的白血病和淋巴瘤，该生物测定中还报告了并发感染。临床和流行病学研究表明，免疫抑制和炎症是非霍奇金淋巴瘤的强烈风险因素，并且流行病学和毒理学研究均表明多氯联苯具有免疫抑制作用并会引发炎症。我们回顾了使用商业多氯联苯产品、单个同系物和同系物混合物进行的已发表的致癌生物测定，重点关注生物测定方案和与免疫相关的观察结果。基于多氯联苯的作用模式框架，我们认为，对于非霍奇金淋巴瘤的观察，可能需要结合多氯联苯暴露进行免疫挑战。我们得出结论，在非霍奇金淋巴瘤方面，人类流行病学与动物生物测定之间缺乏一致性，可能仅仅是所用生物测定方法的结果，而不是基础生物学存在差异。这种缺乏一致性不应被解释为多氯联苯不会增加非霍奇金淋巴瘤发病风险的证据。
