The Effect of L-arginine Ingestion on the Antitumor Action of BCG Instillation In Bladder Carcinoma Induced by N-butyl-N-(4-hydroxybutyl) Nitrosamine in Rats

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

Abstract

PURPOSE: L-arginine is a precursor of nitric oxide(NO). It was reported that administration of L-arginine increases immune reaction in some studies. Also it is known that NO was involved in antitumor effect of BCG therapy on bladder carcinoma. So we tried to know if antitumor effect of intravesical BCG instillation on murine bladder cancer could be potentiated by oral L-arginine administration.
MATERIALS AND METHODS
N-butyl-N-(4-hydroxybutyl) nitrosamine(BBN) was fed to Fisher 344 rats for 20 weeks to induce bladder carcinoma. We instilled intravesically normal saline in group I, BCG in group II, and BCG together with oral ingestion of L-arginine in group III once a week from the 8th week to the 19th week, respectively. Urinary NO secretion was measured. The rats were sacrificed at the 20th week. The expression of inducible nitric oxide synthase(iNOS) as well as the incidence, size and number of bladder tumor was evaluated in the murine bladder.
RESULTS
Urinary NO secretion increased significantly in group II and III compared to group I. The incidence of carcinoma showed no difference among the three groups. The tumors in group II and III were smaller and fewer than those in group I. iNOS was more strongly expressed in group II and III than that in group I. But there was no statistical difference between group II and III on the urinary secretion of NO, the incidence, size and number of the tumor, and the expression of iNOS.
CONCLUSIONS
Our results suggest that ingestion of L-arginine neither enhances production of NO nor potentiates antitumor effect of BCG immunotherapy against bladder carcinoma in this animal model study.