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Carcinogenicity of bucetin in (C57BL/6 X C3H)F1 mice
1Second Department of Pathology, School of Medicine, University of Tokushima, Japan.
Abstract:
The carcinogenicity of bucetin [(3-hydroxy-p-butyrophenetidide) CAS: 1083-57-4], an antipyretic analgesic drug, was examined in 300 (C57BL/6 X C3H)F1 mice. Groups of 50 mice of each sex were treated with 1.5 or 0.75% bucetin in their basal diet for 76 weeks and then fed a basal diet for 8 weeks. Control groups were given a basal diet for 84 weeks. In 10 of 46 (22%) male mice given the high dose of bucetin and in 6 of 45 (13%) given the low dose, renal cell tumors were induced. Dysplastic lesions of the proximal tubules were frequently seen in the males given bucetin in a dose-related fashion. Neither tumorous nor preneoplastic lesions developed in the kidneys of bucetin-treated female mice and control animals. Papilloma of the urinary bladder in 1 male mouse and papillary or nodular hyperplasia in 9 mice of both sexes were observed in groups given the high dose of bucetin.
Insights
Bucetin, an antipyretic analgesic, induced renal cell tumors in male mice in a dose-dependent manner. Female mice and controls showed no kidney tumors, indicating sex-specific carcinogenicity.
Area of Science:
- Toxicology
- Oncology
- Pharmacology
Background:
- Bucetin is an antipyretic and analgesic drug.
- Understanding the long-term effects and potential carcinogenicity of bucetin is crucial for drug safety assessment.
Purpose of the Study:
- To evaluate the carcinogenicity of bucetin in a mouse model.
- To determine if bucetin exposure leads to tumor development and to assess dose-response relationships.
Main Methods:
- 300 (C57BL/6 X C3H)F1 mice (equal sexes) were fed diets containing 1.5% or 0.75% bucetin for 76 weeks, followed by 8 weeks of a basal diet.
- Control groups received only the basal diet for 84 weeks.
- Kidneys and other organs were examined for tumors and preneoplastic lesions.
Main Results:
- Renal cell tumors were induced in 22% of male mice at the high dose and 13% at the low dose.
- Dose-related dysplastic lesions of proximal tubules were frequent in male mice treated with bucetin.
- No kidney tumors or preneoplastic lesions were observed in female mice or control animals.
- Urinary bladder papilloma and hyperplasia were observed in some male mice at the high dose.
Conclusions:
- Bucetin exhibits carcinogenicity in male mice, specifically inducing renal cell tumors.
- The carcinogenic effect of bucetin on the kidney is sex-specific, with males being susceptible and females being resistant.
- These findings highlight the importance of sex as a factor in drug-induced carcinogenicity studies.