Biphasic Increase of Epithelial DNA Synthesis in the Urinary Bladder of Rats Treated with a Tumor Promoter, Sodium L-ascorbate

Sequential changes in the levels of DNA synthesis in urinary bladder epithelium following administration of a rat tumor promoter, sodium L-ascorbate (Na-AsA) for 8 weeks were examined. Male 6-week-old F344 rats were allocated into 4 groups, and given powdered basal diet containing Na-AsA at concentrations of 0 (control), 1.25, 2.5 or 5.0%. The 5-bromo-2'-deoxyuridine (BrdU) labeling index in bladder epithelium in the treated groups increased at week I, but returned to low levels between weeks 2 and 6, and increased at week 8 once again, essentially with dose dependency. The epithelium of the urinary bladder appeared normal at weeks 1 and 2, but slight simple hyperplasia was observed at weeks 4, 6 and 8 with a dose-dependent response. Our results demonstrate that the early DNA synthesis induced in the rat bladder epithelium by Na-AsA is biphasic in nature. (J Toxicol Pathol 2006; 19：53-56)