Ptaquiloside‐induced early‐stage urothelial lesions show increased cell proliferation and intact β‐catenin and E‐cadherin expression

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Abstract
Bracken (Pteridium aquilinum) is a carcinogenic plant whose main toxin, ptaquiloside, causes cancer in farm and laboratory animals. Ptaquiloside contaminates underground waters as well as meat and milk from bracken-grazing animals and is a suspected human carcinogen. A better understanding of the underlying mechanisms of carcinogenesis can be achieved by studying the early stages of this process. Unfortunately, most research on ptaquiloside has focused on the late, malignant, lesions, so the early changes of ptaquiloside-induced carcinogenesis remain largely unknown. This study aims to characterize early-stage ptaquiloside-induced urinary bladder lesions both morphologically and immunohistochemically. 12 male CD-1 mice were administered 0.5 mg ptaquiloside intraperitoneally, weekly, for 15 weeks, followed by 15 weeks without treatment. 12 control animals were administered saline. Bladders were tested immunohistochemically for antibodies against a cell proliferation marker (Ki-67), and two cell adhesion markers (E-cadherin and β-catenin). Two exposed animals died during the work. Six ptaquiloside-exposed mice developed low-grade and two developed high grade urothelial dysplasia. No lesions were detected on control animals. Significantly, increased (p < 0.05) Ki-67 labeling indices were found on dysplastic urothelium from ptaquiloside-exposed mice, compared with controls. No differences were found concerning E-cadherin and β-catenin expression. Early-stage ptaquiloside-induced urothelial lesions show increased cell proliferation but there is no evidence for reduced intercellular adhesiveness, though this may be a later event in tumor progression. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 763–769, 2014.