A STUDY ON THE METABOLISM OF TRYPTOPHAN IN THE URINE OF PATIENTS WITH BLADDER CANCER

Abstract

Industrial bladder cancer in human beings has been shown to be caused by exposure to some aromatic amines. It has been suggested by the results of animal experiments that o-aminophenolic compounds might be the carcinogens. However, the majority of bladder cancer is of non-industrial (spontaneous) origin. Therefore, carcinogenesis of spontaneous bladder cancer has been studied by many authors.
Chemical structures of the known carcinogens for industrial bladder cancer are similar to those of several aromatic amines of tryptophan metabolites. The similarity has directed many researchers' attention to the tryptophan metabolism in spontaneous bladder cancer patients.
In an attempt to relate tryptophan metabolites to spontaneous bladder cancer, urinary excretions of six tryptophan metabolites (3-hydroxyanthranilic acid, 3-hydroxykynurenine, anthranilic acid, xanthurenic acid, kynurenic acid and kynurenine) were measured in 53 patients with urinary tract cancer as well as in 20 control subjects after a test dose of 5.0g l-tryptophan. After operation, the measurements were repeated in 35 of the 53 cases of tumor. The 53 patients with urinary tract cancer consisted of those with bladder cancer (45 cases), those with papillary cancer of the urinary tract (7 cases) and that with ureter lancer (1 case).
In 17 of the 53 tumor patients, urinary β-glucuronidase activity was measured simultaneously with tryptophan metabolites.
The results were as follow:
1) Urinary levels of 3-hydroxyanthranilic acid and 3-hydroxykynurenine were higher in the tumor patients than in the control subjects.
2) The higher urinary levels of 3-hydroxyanthranilic acid and 3-hydroxykynurenine were still maintained after operation.
3) Patients with multiple or recurring tumors had higher 3-hydroxyanthranilic acid and 3-hydroxykynurenine urinary levels than patients with single tumor.
4) More anthranilic acid was excreted in the tumor patients more than in the control subjects, but The difference disappeared after operation
5) Urinary excretion level of xanthurenic acid increased after operation.
6) Urinary β-glucuronidase activity in the tumor patients decreased after operation, and was inhibited considerably by administration of β-glucuronidase inhibitor (SLA) for two weeks.
7) However, there was no relation between the β-glucuronidase activity and the urinary excretion of tryptophan metabolites.