Exposure to perfluorooctanoic acid leads to promotion of pancreatic cancer
By Lisa M Kamendulis, Jessica M Hocevar, Mikayla Stephens, George E Sandusky, and Barbara A Hocevar
Carcinogenesis
January 16, 2022
DOI: 10.1093/carcin/bgac005
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-KRas G12D;Pdx-1 Cre (KC) mouse model of pancreatic cancer. KC mice were exposed to 5ppm 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. While 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 Sod, Cat and TrxR, and a ~3-fold increase in Sod1 mRNA and protein levels at 6 months. While 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.
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