[Fundamental studies on intravesical instillation of carboquone for treatment of urinary bladder tumors--on the effects of intravesical instillation of carboquone in normal beagle dogs].

The effects of intravesical instillation of Carboquone at the clinically used doses of 5 and 10 mg on the normal mucosa of female beagle dogs was compared with that of 10 mg Mitomycin C used as the control drug. Intravesical instillation for 48 hours of 10 mg carboquone/20 ml phosphate buffer solution (PBS) after bilateral cutaneous uretrostomies produced severe inflammatory changes in all layers of the bladder wall. However, no secondary effects were observed in blood laboratory examinations or histological examinations of the whole organ after autopsy. Phosphate buffer solution produced no remarkable secondary effects in animals. Five milligrams carboquone per 20 ml PBS was instilled intravesically once a week for 3 weeks in normal animals. Cystoscopically , the bladder mucosa recovered normally. Blood laboratory examinations showed no abnormal results, but the bladder epithelium had regenerative epithelial hyperplasia and slightly inflammatory changes in the submucosal layers. Two of the three control animals given instillation of 10 mg of Mitomycin C/20 ml PBS had slight leucopenia at 7 days after the last intravesical instillation, but leucocyte count was normal at the end of the experiment. Cystoscopic and histological examination of the epithelium of the urinary bladder revealed severe inflammatory changes in 2 of the 3 animals.

[Effect of carboquone (esquinone) on the development of urinary bladder tumors in rats induced by N-butyl-N-(4-hydroxybutyl) nitrosamine].

The effect of carboquone (CQ) by intraperitoneal administration on the development of urinary bladder tumors in Wistar strain male rats induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) was studied. Urinary bladder tumors were induced in 9 of 11 rats (81.8%) when they were given 0.05% BBN in drinking water for 8 weeks and then given water without BBN for 12 weeks. When CQ 0.25 mg/kg/day was administered intraperitoneally for 7 days after treatment with 0.05% BBN for 8 weeks, incidence of urinary bladder tumors was 19 of 26 rats (73.1%). When CQ 0.25 mg/kg/weekly was given for 12 weeks after treatment with BBN, incidence of urinary bladder tumors was 17 of 27 rats (63.0%). When CQ 0.5mg/kg. B.W./day was given for 7 days after treatment with BBN, tumors developed in the urinary bladder with low incidence as in 8 of 20 rats (40.0%) (P 0.1). When CQ 0.5mg/kg/weekly was given for 12 weeks after treatment of BBN, urinary bladder tumors were induced in 17 of 22 rats (77.3%). Hematotoxity was not observed in any animals treated with CQ. These results showed that CQ inhibited the development of urinary bladder tumors induced by BBN in rats.

[Effect of FT-207 on bladder cancer in rats induced by BBN. II: The effect of oral administration of FT-207 during oncogenesis of bladder cancer].

The effect of Tegafur (FT-207) by oral administration on the development of urinary bladder tumors in Wistar strain male rats induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) was studied. Urinary bladder tumors were induced in 18 of 20 rats (90.0%) when rats were given 0.05% BBN in the drinking water for 8 weeks and then given water without BBN for 12 weeks. When FT-207 100mg/kg B. W./day was given in their diet after treatment with 0.05% BBN for 8 weeks, tumors developed in the urinary bladder with low incidence (9 of 16 rats: 56.3%). Hematotoxicity was not observed in all animals treated with FT-207. These results shows that FT-207 also inhibited the development of urinary bladder tumors treated with BBN in rats by oral administration, which were similar those our previous results showed by intraperitoneal administration of FT-207.