STUDIES ON THE NUCLEIC ACID METABOLISM OF BLADDER CANCER AS NEW ANTI-CANCER DRUGS SENSITIVITY TEST FOR SURGICAL ADJUVANT CHEMOTHERAPY

Abstract

Nucleic acid metabolism was investigated to know the metabolic activites of the bladder carcinoma cells. Surgically obtained specimens were subjected to this investigation radio-acitve nucleic acid precursors, ¹⁴C-Formate via de novo synthetic pathway, and ¹⁴C-8-Adnine via salvage pathway, were used, Activites of bladder carcinoma cell were determined their incorporation rates. The results were as follows:
1) ¹⁴C-Formate incorporation was much higher in grade II, III and IV of bladder carcinoma cells than in the normal epithelium of the bladder, It was also highest in stage B₂ bladder carcinoma cells.
2) ¹⁴C-8-Ademine was found to be incorporated into nucleic acid bases of bladder carcinoma cell. It was considered that as the grades and stages proceded, the incorporation rates became higher.
3) Comparison between the activites of de novo synthesis and salvage pathway was made. The latter was more active than the former in bladder carcinoma cells.
To select most suitable anti-cancer agents for the surgical adjuvant chemotherapy, a new sensitivity test was developed. The prinicple of this test depends on the inhibitory activites of anti-cancer agents on the nucleic acid metabolism. The procedures were the same as those in the incorporation experiment by adding the agents. The results were applied to the 36 patients who underwent total cystectomy or parital cystectomy
1) Mitomycin C and Adriamycin were the most potent agents than Bleomycin, 5-Fluorouracil, Vincristine and Cyclophosphamide on this sensitivity test.
2) Mitomycin C was used for the post-operative adjuvant chemotherapy. Mitomycin C-sensitive patients showed superior results as to local recurrence and metastases to the Mitomycin C-insensitive patients.
3) This new sensitivity test was considered useful for selection of sutiable anti-cancerr agents for surgical chemotherapy of bladder cancer.