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Studies on Tryptophan Metabolism in Patients with Bladder Cancer¹

Department of Medicine [S.G., A.N., P.S.] and Urology [G.M., G.K.], Roswell Park Memorial Institute, Buffalo, New York 14203

Measurement, after 2 g L-tryptophan load p. o., of urinary excretion of some of the metabolites of the tryptophan-niacin pathway was performed on 36 patients with bladder cancer. Assay of hepatic tryptophan pyrrolase activity was done on 21 patients, and assay of kynureninase was done on all patients. Of these patients, increased excretion of kynurenine was found in 12,3-hydroxykynurenine was found in 25, kynurenic acid was found in 9, xanthurenic acid was found in 4, and acetylkynurenine was found in 10. There was no correlation between tryptophan pyrrolase activity and the level of the urinary excretion of tryptophan metabolites, while patients with low kynureninase activity tended to excrete increased quantities of these metabolites. Depressed kynureninase activity and increased excretion of tryptophan metabolites were more marked in the more advanced Stage D₁ and D₂ bladder cancer. Measurements of excretion of the tryptophan metabolites 6 to 12 months after eradication of the disease in 19 patients showed a statistically significant decrease in the excretion of kynurenine, while increased excretion of 3-hydroxykynurenine persisted in 9 of the patients. The excretion of the other metabolites was within normal range in all the patients postoperatively. Similar measurements on two other patients with known evidence of metastases showed an increase in the excretion of the various metabolites in the post-operative compared to the preoperative measurements.

¹ This investigation was supported by USPHS Research Grant CA-5834 from the National Cancer Institute.

Received 5/25/72. Accepted 2/15/73.