Urological Research

, Volume 22, Issue 4, pp 239–245 | Cite as

Effects of sequential intravesical administration of mitomycin C and bacillus Calmette-Guérin on the immune response in the guinea pig bladder

  • L. T. M. Balemans
  • P. D. J. Vegt
  • P. A. Steerenberg
  • E. C. De Boer
  • A. Van Swaaij
  • R. E. M. De Vries
  • A. P. M. Van Der Meijden
  • W. Den Otter
Original Paper


It has been suggested that intravesical treatment with mitomycin C (MMC) before instillation of bacillus Calmette-Guérin (BCG) improves the antitumor activity of BCG in human bladder cancer. Therefore, we studied the immunological effects of sequential intravesical treatment with MMC and BCG in the guinea pig. Four weekly intravesical instillations with MMC preceded six weekly intravesical BCG instillations. The delayed-type hypersensitivity (DTH) skin reaction evoked by tuberculin purified protein derivative (PPD) in guinea pigs receiving BCG intravesically appeared slightly earlier in animals pretreated intravesically with MMC than in phosphatebuffered saline (PBS)-pretreated animals. However, after completing BCG instillations no differences in DTH reaction were observed between these treatment groups. The extent of the local inflammatory reaction in the bladder wall, as well as the parameters measured in the draining iliacal lymph nodes (i.e., the weight, the number of leukocytes, and the composition of leukocyte, subpopulations), did not differ in animals treated with GCG alone or in combination with MMC. A slight increase in the MHC class II expression on the bladeer urothelium was shown if MMC and BCG treatment was combined. The adherence of mycobacteria to the bladder wall, measured using 3H-labeled mycobacteria, dit not differ between MMC/BCG-and BCG-treated animals. We conclude that MMC does not enhance the immune response against mycobacteria. Therefore, we hypothesize that a possible increased antitumor activity by the combination of MMC and BCG might be due to separate, rather than synergistic, effects of the drugs, namely a cytostatic effect of MMC on tumor cells and a local immune response in the bladder evoked by BCG.

Key words

Mitomycin C Bacillus Calmette-Guérin Superficial bladder cancer Guinea pig 


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Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • L. T. M. Balemans
    • 1
    • 2
  • P. D. J. Vegt
    • 3
  • P. A. Steerenberg
    • 1
  • E. C. De Boer
    • 1
  • A. Van Swaaij
    • 1
  • R. E. M. De Vries
    • 1
  • A. P. M. Van Der Meijden
    • 4
  • W. Den Otter
    • 1
    • 2
  1. 1.Laboratory for PathologyNational Institute of Public Health and Environmental Protection (NIPHEP)BilthovenThe Netherlands
  2. 2.Department of PathologyUniversity HospitalUtrechtThe Netherlands
  3. 3.Department of Urology, St.Elisabeth HospitalLeiderdorpThe Netherlands
  4. 4.Department of UrologyGroot-Ziekengasthuis's-HertogenboschThe Netherlands

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