title: Methodological limitations may prevent the observation of non-Hodgkin's lymphoma in bioassays of polychlorinated biphenyls.
abstract: 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.
authors.affiliation: H. Strauss Associates, Inc., Natick, Massachusetts 01760, USA. harleestrauss@verizon.net
authors.forename: Harlee S
authors.initials: HS
authors.lastname: Strauss
authors.forename: Wendy
authors.initials: W
authors.lastname: Heiger-Bernays
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007165:Immunosuppression Therapy; D008228:Lymphoma, Non-Hodgkin / Q000139:chemically induced* / Q000453:epidemiology; D051379:Mice; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051381:Rats; D015203:Reproducibility of Results; D018570:Risk Assessment; D013045:Species Specificity; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D002273:Carcinogens; D011078:Polychlorinated Biphenyls