Intravesical bacillus Calmete-Guerin (BCG) therapy for superficial bladder carcinoma is believed to exert its antitumor effects through immune mechanisms which have yet to be more clearly defined. Recently, BcG infection is known to induce nitric
oxide
(NO) production by macrophages through a T cell mediated process. NO is known to be microbicidal and tumoricidal. Therefore, we studied the effects of intravesical BCG instillation on the induction of inducible NO synthase (iNOS) which is
responsible
for the production of NO in the vesical tissue of rat.
Forty Sprauge-Dawley temale rate were equally divided into 5 groups. In group 1, normal saline (0.85 ml/kg) was intravesically instilled one time. In group 2 and group 3, BCG of Pasteur strain (2 mg/kg, normal saline 0.85 ml/kg) was instilled one
time
and 3 times weekly respectively. In group 4, 10-fold dose of the strain (20 mg/kg, 0.85 ml/kg) and in group 5, 1/10-fold dose of the strain (0.2 mg/kg, 0.85 ml/kg) were instilled one time respectively. We sacrificed two rats to excise the
bladders
in
each group 1, 3, 7, and 14 days after the instillation (after the last instillation in group 3).
INOS mRNA was not detected in the vesical tissues from the rats of group 1, whereas it was strongly detected in all the vesical tissues from the rats in group 2, 3, or 4. More iNOS mRNA was detected 14 days after the instillation in group 3 than
group 2
or 4. In group 5, iNOS mRNA was weakly dotected 1, 3, and 7 days and not dtected 14 days after the instillation.
Our results indicate that intravesical BCG instillation of rat induces the expression of iNOS mRNA in the vesical tissue and suggest that the duration and degree of iNOS mRNA expression is dependant on the dose of BFCG nd the frequency of the
instillations. On the basis of these observations, we conclude that adequate dose and frequency are required for effective treatment of superficial bladder carcinoma in the intravesical BCG thereapy.
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