Lack of Enhanced Epithelial Cell Proliferation in the Urinary Bladder of Heterozygous p53 Knockout Mice Given Sodium Ortho-phenylphenate or Uracil

Abstract

In the present study, we investigated epithelial cell proliferation in heterozygous p53 knockout (p53^+/-) mice after administration of two urinary bladder non-genotoxic carcinogens, in comparison with that in wild-type littermates (p53^+/+). Mice at 10-weeks of age were given 2% sodium ortho-phenylphenate (Na-OPP) or 2.5% uracil in the basal diet for 4 weeks. Uracil evoked a marked elevation of epithelial cell proliferation and development of papillary or diffuse epithelial hyperplasia associated with calculus formation in p53^+/- as well as p53^+/+ mice. Administration of Na-OPP caused alkalization of the urine in both. Neither Na-OPP nor uracil induced a higher epithelial cell proliferative response in p53^+/- mice as compared with p53^+/+ mice. While we previously reported p53^+/- mice to be highly sensitive to a genotoxic urinary bladder carcinogen, N-butyl-N-(4-hydroxybutyl)nitrosamine, the present results suggest that p53^+/- mice may not have a high susceptibility to induction of urinary bladder tumors by non-genotoxic carcinogens.