Effect of intravesical instillation of antitumor drugs in the development of N-butyl-N-(4-hydroxybutyl) nitrosamine-induced bladder tumors in rats

Abstract

F334ラット115匹に0.05%BBNを20週間経口投与し, 同時にADM, CDDP, 生食水の膀胱内注入療法を5週毎に5回連続群(type A, 計20回)週1回群(type B, 計20回)に分け施行した.コントロール群はBBN投与のみとした.40週後に屠殺し検討した.Type Aの生食群はコントロール群におよびtype Bの生食群に比較し有意に膀胱腫瘍重量が増加していた.Type AのADM, CDDP, 膀注群はtype Bの同群より膀胱腫瘍重量が増加していた.ADM, CDDP, 群は2つのtypeでコントロール群に比較し膀胱腫瘍重量の減少した例と増加した例が見られた.組織学的に各群間に差はなかったが, type AのADM群にhigh stage例が多く見られた

We examined the effects of intravesical instillation of adriamycin (ADM) and cis-diammine-dichloroplatinum (CDDP) on the development of bladder tumors induced by 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine in 115 rats. Intravesical instillation was performed in two ways; continuous administration (5 times a week for 5 weeks) and intermittent administration (once a week). Group 1 (control group) did not receive intravesical instillation. Group 2 I(ADM), group 3 (CDDP) and group 4 (physiological saline) were continuous type. Group 5 (ADM), group 6 (CDDP) and group 7 (physiological saline) received intermittent administration. Bladder weight was significantly higher in group 4 than in groups 1 or 7, and that in groups 2 and 3 than that in group 5 and 6. In groups 2, 3, 5 and 6 bladder weight was almost normal or higher than in the control group, and in group 3 histologically cancer was not seen in one rat. Physiological saline had promoting activity, and ADM and CDDP had both inhibitory and promoting activities. Also, intravesical instillation itself was suggested to promote tumor development under carcinogenic circumstances. We conclude that intermittent intravesical instillation should be performed to inhibit tumor recurrence and intravesical instillation therapy should not be performed clinically for a long period.