Four commercial PCB mixtures, Aroclors 1016, 1242, 1254, and 1260, have been tested in rats for their potential to cause cancer. All mixtures induced liver tumors when fed to female rats; Aroclor 1260 also induced liver tumors in male rats (1). Several of these tumors were hepatocholangiomas, a rare biliary tract tumor seldom seen in control rats. These mixtures contain overlapping groups of congeners that, together, span the range of congeners most often found in environmental mixtures. Previously, lifetime dietary exposure to commercial mixtures with 60% chlorine induced liver tumors in three rat strains (6-9). Although many of these tumors were benign, sequential morphologic analyses have demonstrated the eventual progression of the benign liver lesions to malignant carcinomas (8). Commercial mixtures with 54% chlorine induced gastrointestinal tumors (10-12). Less-than-lifetime dietary exposure to commercial mixtures with 42-60% chlorine induced precancerous liver lesions in rats and mice (13-18).
Epidemiologic studies have reported similar tumor sites, although the same specific response was not seen across all studies. Capacitor manufacturing workers exposed to a series of commercial mixtures with 41-54% chlorine had increased mortality from liver, gall bladder, and biliary tract cancers (19), gastrointestinal tract cancers (20), or malignant melanoma (21). An analysis of these and a smaller study (22) found the combined results significant for liver, gall bladder, and biliary tract cancers and for malignant melanoma (23). Earlier, petrochemical refinery workers exposed to Aroclor 1254 and other chemicals had significantly increased mortality from malignant melanoma (24). More recently, electric utility workers exposed to PCBs had significantly increased mortality from malignant melanoma and brain cancer (25). Recent case-control studies have found a significant association between non-Hodgkin's lymphoma and PCB concentrations in adipose tissue (26) and serum (27). In a general population, dietary consumption of rice oil accidentally contaminated with PCBs and chlorinated dibenzofurans, which can be formed when PCBs are heated above 270°C (28), was associated with significantly increased mortality from liver cancer and lung cancer (29).
Mechanistic studies have demonstrated tumor-promoting activity in liver or lung from Aroclor 1254 and some congeners with four to six chlorines: tetrachlorobiphenyl congeners PCB-47, -49, -52, and -77 [International Union of Pure and Applied Chemistry (IUPAC) numbering]; pentachlorobiphenyl congeners PCB-105, -118, and -126; and the hexachlorobiphenyl congener PCB-153 (30). Toxicity of some congeners is correlated with induction of mixed-function oxidases: some congeners are phenobarbital-type inducers, some are 3-methylcholanthrene-type inducers, and some have mixed inducing properties (31-33). The latter two groups most resemble chlorinated dibenzo-p-dioxins and dibenzofurans in structure and toxicity (33,34). These congeners contributing to cancer induction can be present in mixtures with either high or low chlorine content (Table 1).
PCBs are absorbed through ingestion, inhalation, and dermal exposure, after which they are transported similarly through the circulation (35), providing a reasonable basis for expecting similar internal effects from different exposure routes. Quantitatively, dermal exposure poses lower risks because PCBs are substantially but incompletely absorbed through the skin (36-39).
Recent research is suggesting mechanisms by which PCBs can contribute to cancer at other sites. One experiment raises concern for PCBs of low chlorine content, finding that dihydroxy metabolites of PCBs with low chlorine content are activated to reactive intermediates that produce oxidative DNA damage (40). These results provide a possible mechanism to support the hypothesis that environmental PCBs may contribute to human breast cancer. Among the case-control studies of non-Hodgkin's lymphoma, one study found an association with both dioxinlike and nondioxinlike congeners (26), and the other found a multiplicative interaction with seropositivity for the Epstein-Barr virus early antigen (27). Because PCBs suppress the immune system and immunosuppression is an established risk factor for non-Hodgkin's lymphoma, immune system suppression may be a possible mechanism for PCB-induced cancer. Other research has associated both dioxinlike and nondioxinlike congeners with toxicity due to endocrine disruption (41,42).
http://ehpnet1.niehs.nih.gov/child1998/full/106p317-323cogliano/cogliano-full.html#sum`