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Oral perfluorooctane sulfonate (PFOS) lessens tumor development in the APC(min) mouse model of spontaneous familial adenomatous polyposis
Department of Medicine, School of Medicine, West Virginia University, Morgantown, USA; Department of Epidemiology, School of Public Health, West Virginia University, Morgantown, USA; West Virginia University, Medical Center Drive, Morgantown, USA.
Department of Medicine, School of Medicine, West Virginia University, Morgantown, USA.
Department of Medicine, School of Medicine, West Virginia University, Morgantown, USA.
Department of Medicine, School of Medicine, West Virginia University, Morgantown, USA.
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2016 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 16, no 1, 942Article in journal (Refereed) Published
Abstract [en]

Background: Colorectal 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 APC(min) 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.

Methods: At 5-6 weeks of age, APC(min) 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.

Results: PFOS 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 (r(2) for linear trend = 0.44 for males, p's <0.001).

Conclusions: The 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.

Place, publisher, year, edition, pages
London, United Kingdom: BioMed Central, 2016. Vol. 16, no 1, 942
Keyword [en]
APCmin mouse, Perfluorooctane sulfonate, PFOS, Colorectal cancer, Dose–response, Gender
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
URN: urn:nbn:se:oru:diva-53878DOI: 10.1186/s12885-016-2861-5ISI: 000389382500001PubMedID: 27927180ScopusID: 2-s2.0-85002974332OAI: oai:DiVA.org:oru-53878DiVA: diva2:1055818
Note

Funding Agency:

NIH U54GM104942

Available from: 2016-12-13 Created: 2016-12-12 Last updated: 2017-01-09Bibliographically approved

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