Weak synergistic effect of uracil and N-butyl-N-(4-hydroxybutyl)nitrosamine on urine composition, epithelial morphology, and DNA synthesis in the urinary bladder of syrian golden hamster

Abstract

Uracil and N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were tested singly and in combination for their ability to influence urine composition, epithelial morphology, and DNA synthesis in the urinary bladder of male Syrian golden hamsters. Continuously for a period of 8 weeks groups consisting of 10–12 animals each, received BBN, administered in the drinking water at 0.05%, uracil, included in the powdered diet at 3%, both or single or no treatment. After 4 weeks, half of the animals in each group were sacrificed and the remainder maintained until week 8. Except for a significant decrease in calcium ion content found in animals given BBN plus uracil at week 4, there were no significant changes in urinary pH, osmolarity and electrolytes in any of the groups at either time point. BBN plus uracil administration did not demonstrate any differences in terms of induction of urinary crystals or simple hyperplasia when compared with uracil or BBN treatments alone. No uracil-induced calculi were found. However, urinary bladder epithelial surface alterations observed by scanning electron microscopy (e.g., formation of short, uniform microvilli and ropy or leafy microridges) and DNA synthesis in the urothelium were greater in the BBN plus uracil treated animals than in the uracil, BBN and control groups. The results suggest a weak synergistic effect of uracil and BBN in inducing proliferation. © 1995, JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY. All rights reserved.