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

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Wimsatt, JeffreyDepartment 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, Morgantown, USA (author)

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

Article/chapterEnglish2016

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2016-12-08
London, United Kingdom :BioMed Central,2016
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LIBRIS-ID:oai:DiVA.org:oru-53878
https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-53878URI
https://doi.org/10.1186/s12885-016-2861-5DOI

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Language:English
Summary in:English

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Subject category:art swepub-publicationtype

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Funding Agency:NIH U54GM104942
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.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Cancer och onkologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology hsv//eng
APCmin mouse
Perfluorooctane sulfonate
PFOS
Colorectal cancer
Dose–response
Gender
Onkologi
Oncology

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Villers, MeghanDepartment of Medicine, School of Medicine, West Virginia University, Morgantown, USA (author)
Thomas, LaurelDepartment of Medicine, School of Medicine, West Virginia University, Morgantown, USA (author)
Kamarec, StaceyDepartment of Medicine, School of Medicine, West Virginia University, Morgantown, USA (author)
Montgomery, CaitlinDepartment of Medicine, School of Medicine, West Virginia University, Morgantown, USA (author)
Yeung, Leo W. Y.,1981-Örebro universitet,Institutionen för naturvetenskap och teknik,Man-Technology-Environment (MTM) Research Centre(Swepub:oru)lyg (author)
Hu, YanqingDepartment of Statistics, West Virginia University, Morgantown, USA (author)
Innes, KimDepartment of Epidemiology, School of Public Health, West Virginia University, Morgantown, USA (author)
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, Morgantown, USADepartment of Medicine, School of Medicine, West Virginia University, Morgantown, USA (creator_code:org_t)

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In:BMC CancerLondon, United Kingdom : BioMed Central16:11471-2407

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By the author/editor: Wimsatt, Jeffrey; Villers, Meghan; Thomas, Laurel; Kamarec, Stacey; Montgomery, Cait ...; Yeung, Leo W. Y. ...; show more...; Hu, Yanqing; Innes, Kim; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

Articles in the publication: BMC Cancer

By the university: Örebro University

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