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Induction of Ornithine Decarboxylase Activity in Mouse Urinary Bladder by L-Tryptophan and Some of Its Metabolites¹

Masahiro Matsushima², Sadamu Takano³, Erdoan Ertürk and George T. Bryan⁴

Division of Clinical Oncology, Department of Human Oncology, Wisconsin Clinical Cancer Center, Madison, Wisconsin 53792

The responses of female noninbred mouse urinary bladder ornithine decarboxylase (EC 4.1.1.17) (ODC) and S-adenosyl-L-methionine decarboxylase (EC 4.1.1.50) (SAMD) activities to L-tryptophan feeding and to topical intraurethral administration of L-tryptophan and some of its urinary metabolites were studied. Mice fed a diet containing 1% L-tryptophan demonstrated significant increases in vesical ODC and SAMD activities as early as 2 weeks after the commencement of the diet. By the end of the third week, ODC and SAMD activities reached peak values of 7- and 3-fold, respectively, significantly greater than the control levels (p < 0.05 and p < 0.01, respectively). Then, enzyme activities gradually decreased but remained at levels significantly higher than those of the control mice until the end of the sixth week when the study was terminated. Topical application by urethral catheter of some urinary tryptophan metabolites was followed by a rapid, transient induction of urinary bladder ODC activity within 5 hr. Statistically significant differences between vehicle controls and xanthurenic acid (p < 0.01), DL-kynurenine (p < 0.01), L-kynurenine (p < 0.01), anthranilic acid (p < 0.01), and quinaldic acid (p < 0.05) were observed. However, no significant differences were seen with L-tryptophan, 3-hydroxy-DL-kynurenine, the 8-methyl ether of xanthurenic acid, or D-kynurenine or with 3-hydroxyanthranilic, kynurenic, quinolinic, picolinic, and nicotinic acids. Bladder SAMD was not elevated significantly by most of these directly applied tryptophan metabolites. ODC inducibility by active compounds was followed by mucosal hyperplasia within 7 days. These data suggest that certain L-tryptophan metabolites may be involved in two-stage urinary bladder carcinogenesis in a manner similar to that shown to occur in murine skin tumor systems by other chemicals.

¹ Supported in part by Grants CA 11946, CA 14520, and CA 14524 through the National Bladder Cancer Project and by CA 20432 from the National Cancer Institute, NIH. Preliminary reports of this work were made (23, 24).

² Present address: Department of Urology, Toho University School of Medicine, Tokyo 143, Japan.

³ Recipient of a Rotary Foundation Educational Award for International Understanding. Present address: Second Department of Surgery, Kumamoto University Medical School, Kumamoto 860, Japan.

⁴ To whom requests for reprints should be addressed, at Department of Human Oncology, Wisconsin Clinical Cancer Center, University of Wisconsin Center for Health Sciences, K4/528 CSC, 600 Highland Avenue, Madison, Wis. 53792.

Received 6/29/81. Accepted 6/ 7/82.