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Distribution of ¹⁴C-labeled 8-Methyl Ether of Xanthurenic Acid in the Mouse following Bladder Luminal, Subcutaneous, and Intraperitoneal Administration under Carcinogenic Conditions¹

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

The distribution of ¹⁴C-labeled 8-methyl ether of xanthurenic acid (XAE), a human urinary metabolite of the amino acid tryptophan and a urinary bladder carcinogen for the mouse, was studied in mice. Four methods of administration were employed—surgical insertion into the bladder of a cholesterol pellet containing XAE, i.p. injection of XAE, direct instillation into the bladder lumen (i.u.), and s.c. injection into mice with (Group 1) and without (Group 2) cholesterol pellets in their bladders. Following surgical implantation of a pellet containing XAE, in 1–24 hr, 4–41% of the XAE was eluted from the pellets. Most of the ¹⁴C was retained in several tissues or was present in the gastrointestinal contents and feces. The urinary bladder retained much greater quantities of ¹⁴C than did other tissues. When an aqueous solution of XAE was placed i.u. into the mouse bladder, in 24 hr, nearly all disappeared from the bladder lumen. These data indicated that the bladder was permeable to XAE, and had ample opportunity for intimate contact with this compound during the acute period of exposure during the process of carcinogenesis.

Following s.c. administration of XAE to mice of Groups 1 and 2, in 24 hr, more than 95% of ¹⁴C was present in the urine, intestinal contents, feces, and CO₂. The bladder specific activity in both groups was comparable. Thus differences in bladder carcinoma incidence observed previously for mice, similar to those in Groups 1 and 2, appeared unrelated to the quantity of XAE absorbed by the bladder following s.c. injection.

¹ Supported in part by Grant No. CA-10017 from the National Cancer Institute, USPHS, and by Grants Nos. E-115 and E-116H from the American Cancer Society. Presented in part at the Ninth International Cancer Congress, Tokyo, Japan, October, 1966 (Abstracts, IX International Cancer Congress, 146, 1966).

Received 6/26/67. Accepted 10/18/67.