Pancreatic cancer is the fourth leading cause of
cancer deaths in the United States.
Perfluorooctanoic acid (PFOA), a persistent
environmental pollutant, has been shown to induce pancreatic acinar cell
tumors in rats. Human epidemiologic studies have linked PFOA exposure to adverse chronic health effects including several types of
cancer. Previously, we demonstrated that PFOA induces oxidative stress and focal ductal
hyperplasia in the mouse pancreas. Here, we evaluated whether PFOA promotes
pancreatic cancer using the LSL-KRasG12D;Pdx-1 Cre (KC) mouse model of
pancreatic cancer. KC mice were exposed to 5 ppm PFOA in
drinking water starting at 8 weeks of age and analyzed at 6 and 9 months of age. At the 6-month time point, PFOA exposure increased pancreatic intraepithelial
neoplasia (PanIN) area by 58%, accompanied by a 2-fold increase in lesion number. Although PanIN area increased at 9 months, relative to 6 months, no treatment effect was observed.
Collagen deposition was enhanced by PFOA at both the 6- and 9-month time points. PFOA also induced oxidative stress in the pancreas evidenced by elevated
antioxidant activity of
superoxide dismutase (Sod),
catalase and
thioredoxin reductase, and a ~3-fold increase in Sod1
mRNA and
protein levels at 6 months. Although
antioxidant activity was not enhanced by PFOA exposure at the 9-month time point, increased pancreatic oxidative damage was observed. Collectively, these results show that PFOA elicited temporal increases in PanIN lesion area and desmoplasia concomitant with the induction of oxidative stress, demonstrating that it functions to promote
pancreatic cancer progression.