Oral perfluorooctane sulfonate (PFOS) lessens tumor development in the APCmin mouse model of spontaneous familial adenomatous polyposis

BMC Cancer

Research Article

Kim Innes¹  Meghan Villers²  Caitlin Montgomery²  Stacey Kamarec²  Laurel Thomas²  Jeffrey Wimsatt³  Yanqing Hu⁴  Leo W. Y. Yeung⁵ 

[1] Department of Epidemiology, School of Public Health, West Virginia University, 26506, Morgantown, WV, USA;Department of Medicine, School of Medicine, West Virginia University, 26506, Morgantown, WV, USA;Department of Medicine, School of Medicine, West Virginia University, 26506, Morgantown, WV, USA;Department of Epidemiology, School of Public Health, West Virginia University, 26506, Morgantown, WV, USA;West Virginia University, 186 HSCN, 1 Medical Center Drive, 26508, Morgantown, WV, USA;Department of Statistics, West Virginia University, 26506, Morgantown, WV, USA;Man-Technology-Environment (MTM) Research Centre, School of Science and Technology, Örebro University, Fakultetsgatan 1, SE-70182, Örebro, Sweden;

关键词: APC mouse;    Perfluorooctane sulfonate;    PFOS;    Colorectal cancer;    Dose–response;    Gender;   

DOI  :  10.1186/s12885-016-2861-5

 received in 2016-02-17, accepted in 2016-10-11,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundColorectal cancer is the second most common cause of cancer deaths for both men and women, and the third most common cause of cancer in the U.S. Toxicity of current chemotherapeutic agents for colorectal cancer, and emergence of drug resistance underscore the need to develop new, potentially less toxic alternatives. Our recent cross-sectional study in a large Appalachian population, showed a strong, inverse, dose–response association of serum perfluorooctane sulfonate (PFOS) levels to prevalent colorectal cancer, suggesting PFOS may have therapeutic potential in the prevention and/or treatment of colorectal cancer. In these preliminary studies using a mouse model of familial colorectal cancer, the APCmin mouse, and exposures comparable to those reported in human populations, we assess the efficacy of PFOS for reducing tumor burden, and evaluate potential dose–response effects.MethodsAt 5–6 weeks of age, APCmin mice were randomized to receive 0, 20, 250 mg PFOS/kg (females) or 0, 10, 50 and 200 mg PFOS/kg (males) via their drinking water. At 15 weeks of age, gastrointestinal tumors were counted and scored and blood PFOS levels measured.ResultsPFOS exposure was associated with a significant, dose–response reduction in total tumor number in both male and female mice. This inverse dose–response effect of PFOS exposure was particularly pronounced for larger tumors (r2 for linear trend = 0.44 for males, p’s <0.001).ConclusionsThe current study in a mouse model of familial adenomatous polyposis offers the first experimental evidence that chronic exposure to PFOS in drinking water can reduce formation of gastrointestinal tumors, and that these reductions are both significant and dose-dependent. If confirmed in further studies, these promising findings could lead to new therapeutic strategies for familial colorectal cancer, and suggest that PFOS testing in both preventive and therapeutic models for human colorectal cancer is warranted.

【 授权许可】

CC BY   
© The Author(s). 2016