Polychlorinated biphenyls (PCBs) enhance the neoplastic progression of human breast epithelial cells in a xenograft model

Abstract

PCBs have long been suspected as environmental breast carcinogens but the epidemiological evidence has not strongly supported this concern. As an experimental approach to investigate the role of PCBs in breast cancer development, the preneoplastic MCF10AT1 human breast epithelial cell line was used in xenograft experiments. After implantation, MCF10AT1 cells form tubular structures, some of which progress to lesions with the histological features of atypical hyperplasia, ductal carcinoma in situ (DCIS), and invasive carcinoma (IC). MCF10AT1 cells were injected into female Ncr nude mice, and the mice were treated with corn oil, 0.3 or 1 μg/kg/day PCB126 (a coplanar PCB), or 1 or 3 mg/kg/day PCB153 (a non‐coplanar PCB) by gavage for 10 weeks. As indices of PCB exposure, 0.3 and 1 μg/kg/day PCB126 increased hepatic Cyp1a1 mRNA levels by ~40‐and ~1000‐fold while 1 and 3 mg/kg/day PCB153 increased hepatic Cyp2b10 mRNA levels by ~12‐and ~125‐fold. The MCF10AT1 lesions were graded histologically on a scale of 0 (simple tubules) to 5 (IC). 17% of the lesions in the corn oil group were graded at 4 (DCIS) or 5, while 45% and 36% in the 0.1 and 1 μg/kg/day PCB126 groups and 67% and 50% in the 1 and 3 mg/kg/day PCB153 groups were graded at 4 or 5. These results suggest that relatively low doses of PCBs can enhance the neoplastic progression of human breast epithelial cells. Supported by NIH grant (ARRA) 1R21ES016373.