Induction of ornithine decarboxylase activity in mouse urinary bladder by L-tryptophan and some of its metabolites.

The responses of female noninbred mouse urinary bladder ornithine decarboxylase (EC 4.1.1.17) (ODC) and S-adenosylu-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 stud ied. 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 7and 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 com pounds 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.