Comparision of the Effects of Intravesical E. coli or BCG Instillation on Bladder Tumor Induced by N-butyl-N-(4-hydroxybutyl) Nitrosamine in Rats

Kim, Jong Sung; Cho, Myoung Keun; Rim, Joung Sik

Abstract

PURPOSE: Through our previous studies on the antitumor mechanism of BCG therapy for bladder carcinoma, we become to consider a nitric oxide(NO)-mediated process as one of its mechanisms. Briefly describing, intravesical BCG stimulates T helper cells to secrete INF-gammaand also stimulates macrophages to secrete TNF-alpha and IL-1. The cytokines induce expression of inducible NO synthase(iNOS) in the macrophages, the epithelium, and the tumor cells of the bladder , which results in longstanding abundant secretion of NO in those cells and results in apoptosis of tumor cells. Our theory of NO-mediated antitumor mechanism confronts a question; Can E. coli replace BCG because E. coli also induce NO production To reply to the question this study was done.
MATERIALS AND METHODS
N-butyl-(4-hydroxybutyl) nitrosamine was fed in rats. Normal saline in group I, E. coli in group II, and BCG in group III were intravesically instilled weekly for 12 times, respectively. Urinary nitrite concentration was measured in the 3 groups. Observed were histological findings including iNOS expression ,incidence ,size and number of the tumors in the excised bladder at the 20th week.
RESULTS
Urinary nitrite concentration in group III was significantly higher than that in group I and II. iNOS expression was relatively strong in the epithelium and the tumor of group II and III, but weak in those of group I. No statistically significant difference was found in the incidence of tumor among the three groups. Induced tumors were fewer in group II and III than in group I. And the tumors were smaller in group III than in group II.
CONCLUSIONS
Intravesical E. coli instillation showed less significant secretion of NO in the bladder than BCG instillation. Intravesical E. coli might weakly suppress tumor growth in the rats. On the other hand, intravesical BCG instillation induces strong iNOS expression and significant NO production in the bladder tissue and seems to suppress tumor growth.