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Suppression of rat urinary bladder carcinogenesis by alpha-difluoromethylornithine
1Department of Urology, Faculty of Medicine, University of Tokyo, Japan.
Abstract:
The inhibitory effect of oral administration of alpha-difluoromethylornithine (DFMO) on urinary bladder carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)-nitrosamine (BHBN) was explored. Since DFMO in the drinking water at 0.5% and 0.2% had been demonstrated to inhibit tumorigenesis, lower doses (0.2%, 0.1%, 0.03% and 0.01%) of DFMO were examined in the present study. After six-week treatment with the drinking water containing 0.05% BHBN, water containing DFMO at 0.2%, 0.1%, 0.03%, 0.01% or 0% was administered during the subsequent 34 weeks. Incidence of bladder carcinoma was 15/35 (43%), 14/35 (40%), 21/35 (60%), 20/35 (57%) and 27/35 (77%) in the 0.2%, 0.1%, 0.03%, 0.01% and 0% DFMO groups, respectively. Stastistical analysis indicated significant tumor suppression in the 0.2% and 0.1% DFMO groups. Tumor multiplicity and size were not affected by DFMO treatment. No untoward effects were demonstrated in body weight gain or examination of pertinent organs. Our data indicate that bladder carcinogenesis induced by six-week exposure to 0.05% BHBN is significantly inhibited by daily administration of DFMO at the level of 0.1% or higher in drinking water.
Insights
Oral administration of alpha-difluoromethylornithine (DFMO) significantly inhibited bladder cancer in rats induced by N-butyl-N-(4-hydroxybutyl)-nitrosamine (BHBN). Lower DFMO doses showed effectiveness, with no adverse effects on body weight or organs.
Area of Science:
- Oncology
- Chemoprevention
- Urothelial Carcinogenesis
Background:
- N-butyl-N-(4-hydroxybutyl)-nitrosamine (BHBN) is a known inducer of urinary bladder cancer.
- Previous studies indicated that alpha-difluoromethylornithine (DFMO) at 0.5% and 0.2% inhibits BHBN-induced tumorigenesis.
Purpose of the Study:
- To investigate the inhibitory effects of lower doses of DFMO on urinary bladder carcinogenesis induced by BHBN.
- To determine the minimum effective dose of DFMO for chemoprevention against BHBN-induced bladder tumors.
Main Methods:
- Rats were exposed to 0.05% BHBN in drinking water for six weeks.
- Following BHBN exposure, rats received drinking water containing varying concentrations of DFMO (0.2%, 0.1%, 0.03%, 0.01%) or no DFMO for 34 weeks.
- Tumor incidence, multiplicity, size, body weight, and organ examination were assessed.
Main Results:
- Significant suppression of bladder carcinoma incidence was observed in groups receiving 0.2% and 0.1% DFMO.
- Tumor incidence was 43% and 40% for 0.2% and 0.1% DFMO groups, respectively, compared to 77% in the control group.
- DFMO treatment did not affect tumor multiplicity or size, nor did it cause adverse effects on body weight gain or organ health.
Conclusions:
- Daily oral administration of DFMO at 0.1% or higher in drinking water significantly inhibits bladder carcinogenesis induced by BHBN exposure.
- DFMO demonstrates chemopreventive potential against BHBN-induced bladder cancer without significant side effects.