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The Metabolism of the 8-Methyl Ether of Xanthurenic Acid in the Mouse¹

The Division of Clinical Oncology, University of Wisconsin Medical School, Madison, Wisconsin 53706

The metabolism of the ¹⁴C-labeled 8-methyl ether of xanthurenic acid (XAE), a human urinary metabolite of the amino acid tryptophan and a urinary bladder and lymphoreticular carcinogen for the mouse, was studied in stock mice and mice maintained under carcinogenic conditions. In all instances, XAE was found to be rapidly excreted by the mouse with about 95% of the administered dose being excreted in urine, feces, and CO₂ within 24 hours. Data suggest that XAE is dehydroxylated to 8-methoxyquinaldic acid, decarboxylated to 4-hydroxy-8-methoxyquinoline, and also converted to a third unidentified metabolite. However, the total of these three metabolites amounted to less than 1% of recovered urinary radioactivity, with over 99% being recovered as unchanged XAE in both stock mice and mice maintained under carcinogenic conditions. Mice maintained under carcinogenic conditions displayed an increased capacity for decarboxylation, suggesting an adaptive response to chronic administration of XAE. However, no concomitant increase in urinary metabolites was observed. The significance of this adaptive response and the apparent metabolic inertness of XAE in mice is discussed in relation to its carcinogenic activity for the mouse urinary bladder and lymphoreticular system.

¹ Supported in part by Grant No. CA-10341 from the National Cancer Institute, USPHS, and by Grant No. E-485 from the American Cancer Society.

² Career Development Awardee of the National Cancer Institute, USPHS (1-K4-CA-8245-01A1).

Received 8/16/68. Accepted 12/22/68.