Induction of squamous cell carcinoma in the mandible and maxilla, and, Reproductive dysfunction in mink (Mustela vison) caused by 3,3',4,4',5-pentachlorobiphenyl (PCB 126)

The hypothesis of this dissertation is that the lesion induced by 3,3 ',4,4',5-pentachlorobiphenyl (PCB 126), identified as squamous epithelial proliferation in the maxilla and mandible of mink (Mustela vison), is oral squamous cell carcinoma. The objectives of this study were to determine the progression of the lesion after removal of the stimulus (PCB 126), and the ability of the cells comprising the lesion to form a tumor after being transplanted or injected into nude, athymic mice. The lesion was histologically detectable in mink exposed to 24 mug PCB 126/kg feed for one to six weeks, and was clinically detectable in the PCB 126-exposed mink of the three-, four-, and five-week groups, by 12-weeks post-treatment. The lesion worsened during the six or eight-month post-exposure period in 100% of the mink in all exposure groups, thus meeting the first criteria of lesion progression after withdrawal of the PCB 126 stimulus. In the athymic mouse trial, nodular growths were observed in two of the 18 mice that were implanted with gingiva from the oral lesion of PCB 126-exposed mink. Although the tumors in the mice were classified as non-malignant, the origin was non-host (mink) stratified squamous epithelium, demonstrating consistency with neoplastic criteria. Another objective of the study was to determine if the oral neoplasia caused systemic osteolysis in addition to local osteolysis of the jawbones in PCB 126-exposed mink. A series of radiographs evaluated dental alignment, bone lysis, nail growth, organ integrity and seven skull and subcutaneous fat measurements of PCB 126-exposed and control mink. In addition, calcium and phosphorus content of femurs were assessed. Radiographs revealed that PCB 126 caused severe localized mandibular and maxillary osteolysis that aggressively progressed into the zygoma and nasal turbinates. However, systemic effects of PCB 126 on bone were not observed in this study, and there were no significant changes in femur calcium or phosphorus content. In addition to the oral lesion assessments, a study was conducted to determine the reproductive effects of PCB 126 in female mink. No reproductive effects were observed at 0.24 mug PCB 126/kg feed. However, total reproductive failure occurred at dietary concentrations as low as 2.4 mug PCB 126/kg feed. A number of changes in clinical, hematological and serum chemistry parameters were observed in both the adult female and juvenile mink exposed to PCB 126.; Wild mink naturally exposed to environmental contaminants were also assessed for the prevalence of the oral neoplasia. Four of nine mink trapped in a PCB-contaminated, Superfund site exhibited histological evidence of the oral lesion. There was a significant correlation between the severity of the lesion and hepatic concentrations of total PCBs and 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents in these mink. Results from these experiments indicate that PCB 126 induces an extremely invasive and destructive form of oral squamous cell carcinoma, as well as other adverse effects in mink.