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.