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Untersuchungen über den Tryptophan-Stoffwechsel beim Blasen-Carcinom

Studies about the tryptophan metabolism in the carcinoma of bladder

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Summary

The urines of two healthy persons and of two patients with bladder carcinoma were analysed in two different methods with regard to possible conjugates of tryptophan metabolites. In both cases the metabolites in question were to be found in free form. The tryptophan metabolites, eliminated in urine, are determinated in healthy individuals (20 to 30 years of age). The same examinations are carried out on patients with urinary bladder carcinoma. The elimination of one or more metabolites is found increased.

Bladder carcinoma are induced in rats through the implantation of cholesterol pellets which contained 4–5 mg 3-hydroxy-anthranilic acid. 30 rats were treated and after a period of 8–10 months it was found that 25 rats had developed tumors; 7 of which were carcinoma.

3-hydroxy-anthranilic acid-[3H] was instilled into the bladder of healthy rats. 20 to 30% were absorbed within 2 to 6 hours. The metabolite was not deposited into the bladder wall itself. After the intraveneous injection of 3-hydroxy-anthranilic acid-[3H] into rats, bearing bladder tumors, it was found to be incorporated in the tumor tissue, where its presence was clearly shown in radiohistological studies. A patient without bladder ailments who was given 3-hydroxy-anthranilic acid-[3H] eliminated 80% of the dosis within 3 days, while a patient with bladder carcinoma eliminated barely 50%.

Zusammenfassung

Der Urin von 2 normalen Personen und von 2 Trägern von Blasencarcinomen wurde auf Konjugatbildungen von Tryptophan-Metaboliten (Kynurenin, 3-Hydroxy-kynurenin, Kynurensäure, Xanthurensäure, Anthranilsäure und 3-Hydroxyanthranilsäure) nach zwei verschiedenen Methoden untersucht. In beiden Fällen lagen die untersuchten Metaboliten in freier Form vor. Bei Blasencarcinom-Patienten wurde eine erhöhte Ausscheidung eines oder mehrerer Metaboliten beobachtet.

Durch Implantation von Cholesterinkugeln, die 4–5 mg 3-Hydroxy-anthranilsäure enthalten, in die Harnblase von Ratten werden bei 30 Tieren nach 8–10 Monaten Inkubationsdauer 25 Tumoren, darunter 7 Carcinome, ausgelöst.

Nach Instillation von 3-Hydroxy-anthranilsäure-[3H] in die Blase gesunder Ratten werden innerhalb von 2–6 Std 20–30% resorbiert, die Blasenwand selbst zeigt keinen Einbau der Substanz. Nach i.v. Injektion von 3-Hydroxy-anthranilsäure-[3H] zeigt sich bei Ratten, die einen Blasentumor tragen, ein Einbau in den Tumor, der u. a. im radiohistologischen Schnitt eindeutig nachgewiesen werden kann. Bei einem blasengesunden Patienten wird 3-Hydroxy-anthranilsäure-[3H] i.v. injiziert. Nach 3 Tagen sind 80% der Dosis im Urin ausgeschieden worden. Bei einem Blasencarcinom-Patienten betrug die Ausscheidung nur knapp 50%.

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Literatur

  • Benassi, C. A., Veronese, F. M., Antoni, A.: On the determination of small amounts of tryptophan metabolites and their occurrence in normal human urine. Clin. chim. Acta 17, 383 (1968).

    Google Scholar 

  • Boyland, E., Williams, D. C.: The estimation of tryptophan metabolites in the urine of patients with cancer of the bladder. Biochem. J. 60, V (1955).

    Google Scholar 

  • ——: The metabolism of tryptophan in patients suffering from cancer of the bladder. Biochem. J. 64, 578 (1956).

    Google Scholar 

  • Boyland, E., Wallace, D. M., Williams, D. C.: Inhibition of urinary β-glucuronidase of patients with cancer of the bladder by oral administration of 1.4. Saccharolactone and related compounds. Brit. J. Cancer 11, 578 (1957).

    Google Scholar 

  • Boyland, E., Wallace, D. M., Avis, P. R. D., Kindler, C. H.: Attempted prophylaxis of bladder cancer with 1.4. Glucosaccharolactone. Brit. J. Urol. 36, 563 (1964).

    Google Scholar 

  • Brown, R. R., Price, J. M., Wear, J. B.: The metabolism of tryptophan in bladder cancer patients. Proc. Am. Ass. Cancer Res. 2, 7 (1955).

    Google Scholar 

  • Brown, R. R., Price, J. M.: Quantitative studies in metabolites of tryptophan in the urine of the dog, cat, rat and man. J. biol. Chem. 219, 985 (1956).

    Google Scholar 

  • Bryan, G. T., Brown, R. R., Price, J. M.: Mouse bladder carcinogenity of certain tryptophan metabolites and other aromatic nitrogen compounds suspended in cholesterol. Cancer Res. 24, 596 (1964).

    Google Scholar 

  • ———: Absorption of 14C-labeled 3-hydroxy-l-kynurenine and 3-hydroxy-anthranilic-acid from the mouse urinary bladder under carcinogenic conditions. Cancer Res. 25, 1432 (1965).

    Google Scholar 

  • Dalgliesh, C. E.: The relation between pyridoxin and tryptophan metabolism, studied in the rat. Biochem. J. 52, 3 (1952).

    Google Scholar 

  • Dunning, W. F., Curtis, M. R., Maun, M. E.: The effect of added dietary tryptophan on the occurrence of 2-acetylamino-fluorene-induced liver and bladder cancer in rats. Cancer Res. 10, 454 (1950).

    Google Scholar 

  • Hochberg, K., Kochen, W., Röhl, L.: Biochemische und autoradiographische Untersusungen zur Ätiologie des Blasen-Carcinoms. Verh. Ber. dtsch. Ges. Urol. 22, 1968 (1969 im Druck).

    Google Scholar 

  • Kochen, W., Lauer, G.: Eine elektronisch gesteuerte Apparatur zur vollständigen Automatisierung der Säulenchromatographie. Chromatographia, H. 5, 1969, 213.

  • Kochen, W.: Die gas-chromatographische Trennung und quantitative Bestimmung der Tryptophan-Metaboliten. Chromatographia 1970 (im Druck).

  • Michael, A. F., Drummond, K. N., Doeden, D., Anderson, J. A., Good, R. A.: Tryptophan metabolism in man. J. clin. Invest. 43, 1730 (1964).

    Google Scholar 

  • Morris, G., Bryan, G. T.: Absorption of 14C-labeled tryptophan, its metabolites and glycin and glucose by the urinary bladder of the mouse. Invest. Urol. 3, 577 (1966).

    Google Scholar 

  • Price, J. M., Brown, R. R., Curreri, A. R., McIver, F. A.: Tryptophan metabolites in patients with neoplastic disease. Clin. Res. Proc. 3, 201 (1955).

    Google Scholar 

  • ——, McIver, F. A., Curreri, A. R.: Tryptophan metabolism in patients with cancer. Proc. Amer. Ass. Cancer Res. 2, 140 (1956).

    Google Scholar 

  • ——, Larson, F. C.: Quantitative studies on human urinary metabolites of tryptophan as affected by isoniazid and desoxypyridoxine. J. clin. Invest. 36, 1600 (1957a).

    Google Scholar 

  • ——, Rukavina, J. G., Mendelson, C., Satter, E. J., Olson, C.: Scleroderma (acrosclerosis): II. tryptophan metabolism before and during treatment by chelation (EDTA). J. Invest. Dermat. 29, 289 (1957b).

    Google Scholar 

  • ——, Ellis, M. E.: Quantitative studies on the urinary excretion of tryptophan metabolites by humans ingesting a constant diet. J. Nutr. 60, 323 (1956).

    Google Scholar 

  • Price, J. M., Disorders of tryptophan metabolism. Univ. of Michigan Medical Bull. 1958 Vol. XXIV, pp 461–485.

  • —: Studies on etiology of carcinoma of urinary bladder. J. Urol. 83, 376 (1960).

    Google Scholar 

  • Röhl, L.: Prostatic and bladder tumors studied in vitro on the response to adrenosterone and on o-aminophenol. Vortrag: VIII. Intern. Krebskongreß, Moskau 1962.

  • Satoh, K., Price, J. M.: Fluorometric determination of kynurenic- and xanthurenic acid in human urine. J. biol. Chem. 230, 781 (1958).

    Google Scholar 

  • Taugner, R., Wagenmann, U.: Serienmäßige Herstellung von Gefrierschnitt-Autoradiogrammen mit optimalem Kontakt. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 234, 336 (1958).

    Google Scholar 

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Kochen, W., Hochberg, K. Untersuchungen über den Tryptophan-Stoffwechsel beim Blasen-Carcinom. Z Krebs-forsch 73, 251–264 (1970). https://doi.org/10.1007/BF00524406

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  • DOI: https://doi.org/10.1007/BF00524406

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