title: Oral perfluorooctane sulfonate (PFOS) lessens tumor development in the APCminmouse model of spontaneous familial adenomatous polyposis.
abstract: 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 APCminmouse, 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.
  
  
  
  At 5-6 weeks of age, APCminmice 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.
  
  
  
  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 (r2for linear trend = 0.44 for males, p's <0.001).
  
  
  
  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.
authors.affiliation: Department of Medicine, School of Medicine, West Virginia University, Morgantown, WV, 26506, USA. jefwimsatt@gmail.com.|Department of Epidemiology, School of Public Health, West Virginia University, Morgantown, WV, 26506, USA. jefwimsatt@gmail.com.|West Virginia University, 186 HSCN, 1 Medical Center Drive, Morgantown, WV, 26508, USA. jefwimsatt@gmail.com.
authors.forename: Jeffrey
authors.identifier: 0000-0002-7818-2479
authors.initials: J
authors.lastname: Wimsatt
authors.affiliation: Department of Medicine, School of Medicine, West Virginia University, Morgantown, WV, 26506, USA.
authors.forename: Meghan
authors.initials: M
authors.lastname: Villers
authors.affiliation: Department of Medicine, School of Medicine, West Virginia University, Morgantown, WV, 26506, USA.
authors.forename: Laurel
authors.initials: L
authors.lastname: Thomas
authors.affiliation: Department of Medicine, School of Medicine, West Virginia University, Morgantown, WV, 26506, USA.
authors.forename: Stacey
authors.initials: S
authors.lastname: Kamarec
authors.affiliation: Department of Medicine, School of Medicine, West Virginia University, Morgantown, WV, 26506, USA.
authors.forename: Caitlin
authors.initials: C
authors.lastname: Montgomery
authors.affiliation: Man-Technology-Environment (MTM) Research Centre, School of Science and Technology, Örebro University, Fakultetsgatan 1, Örebro, SE-70182, Sweden.
authors.forename: Leo W Y
authors.initials: LW
authors.lastname: Yeung
authors.affiliation: Department of Statistics, West Virginia University, Morgantown, WV, 26506, USA.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Epidemiology, School of Public Health, West Virginia University, Morgantown, WV, 26506, USA.
authors.forename: Kim
authors.initials: K
authors.lastname: Innes
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D025601:Adenomatous Polyposis Coli Protein / Q000502:physiology*; D000284:Administration, Oral; D017738:Alkanesulfonic Acids / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005466:Fluorocarbons / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D017738:Alkanesulfonic Acids; D005466:Fluorocarbons; C000613192:adenomatous polyposis coli protein, mouse; C076994:perfluorooctane sulfonic acid
keywords: APCmin mouse; Colorectal cancer; Dose–response; Gender; PFOS; Perfluorooctane sulfonate