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Species differences in sodium o-phenylphenate induction of urinary bladder lesions
R Hasegawa1, S Takahashi, M Asamoto
1First Department of Pathology, Nagoya City University Medical School, Japan.
Abstract:
The effects of sodium o-phenylphenate (Na-OPP) treatment on urinary bladder epithelium were examined in male F344 rats, B6C3F1 mice, Syrian golden hamsters and Hartley guinea pigs. Na-OPP was incorporated into diet at a dose of 2% and administered for 4, 8, 12, 24, 36 or 48 weeks. Simple and papillary or nodular (PN) hyperplasias were evident on light microscopy and pleomorphic microvilli demonstrated by scanning electron microscopy were only observed in rats, the lesions becoming more advanced with continued chemical feeding. In mice, hamsters and guinea pigs, proliferative lesions relating to Na-OPP administration were not observed. No significant differences in urinary pH, osmolality or crystal formation were apparent between the various animal species. Since carcinogenicity has been demonstrated for Na-OPP in rats but not in mice, the present findings suggest that Na-OPP might not exert urinary bladder carcinogenic potential in hamsters and guinea pigs.
Insights
Sodium o-phenylphenate (Na-OPP) caused urinary bladder epithelial changes in rats but not in mice, hamsters, or guinea pigs. These findings suggest Na-OPP may not be a urinary bladder carcinogen in hamsters and guinea pigs.
Area of Science:
- Toxicology
- Urothelial Biology
- Comparative Pathology
Background:
- Sodium o-phenylphenate (Na-OPP) is a chemical with demonstrated carcinogenicity in rats.
- Understanding species-specific responses to Na-OPP is crucial for risk assessment.
Purpose of the Study:
- To investigate the effects of Na-OPP on urinary bladder epithelium across different species.
- To compare the urothelial response to Na-OPP in rats, mice, hamsters, and guinea pigs.
Main Methods:
- Dietary administration of 2% Na-OPP to male F344 rats, B6C3F1 mice, Syrian golden hamsters, and Hartley guinea pigs for up to 48 weeks.
- Evaluation of urinary bladder epithelium using light microscopy and scanning electron microscopy.
- Analysis of urinary parameters including pH, osmolality, and crystal formation.
Main Results:
- Rats exhibited simple and papillary/nodular hyperplasias and pleomorphic microvilli, with lesion severity increasing with exposure duration.
- Mice, hamsters, and guinea pigs did not develop proliferative lesions in response to Na-OPP.
- No significant interspecies differences in urinary pH, osmolality, or crystal formation were observed.
Conclusions:
- Na-OPP induces urothelial proliferative lesions specifically in rats.
- The absence of lesions in mice, hamsters, and guinea pigs suggests a species-specific mechanism of toxicity.
- These findings indicate Na-OPP may lack urinary bladder carcinogenic potential in hamsters and guinea pigs, contrasting with its known effects in rats.