Abstract
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.
Highlights
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
Toxicity of current chemotherapeutic agents for colorectal cancer, and ongoing challenges with drug resistance suggest that new drug approaches continue to have value [2, 3]
In a cross-sectional study in a large Ohio Valley cohort, we investigated the potential link between prevalent colorectal cancer and serum perfluorooctane sulfonate (PFOS) [12]
Summary
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 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. If shown of benefit, at low doses, PFOS could suggest a novel mechanism for treating colorectal cancer
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