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Effect of L-Tryptophan Excess and Vitamin B₆ Deficiency on Rat Urinary Bladder Cancer Promotion¹

The Eppley Institute for Research in Cancer [D. F. B., A. D. J., S. M. C.] and Department of Pathology and Microbiology, College of Medicine [R. H., M. S. J., S. M. C.], University of Nebraska Medical Center, Omaha, Nebraska 68105-1065

To further evaluate the role of tryptophan and vitamin B₆ in bladder carcinogenesis, male Fischer 344 rats were fed 0.2% N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) in semipurified diet or were given semipurified diet alone for 4 weeks. One week later, rats from each group were assigned for the remainder of the experiment to one of four experimental diets, labeled as follows: group 1, control semipurified; group 2, L-tryptophan excess (2%); group 3, vitamin B₆-deficient (1.0 mg/kg diet); or group 4, L-tryptophan excess, plus vitamin B₆-deficient diet. All surviving rats were killed at 80 weeks of the experiment. Throughout the study, body weights were reduced in the groups fed FANFT and, at 70 and 80 weeks, body weights were reduced in the groups given tryptophan excess. The incidence of urinary bladder carcinoma was highest in the group treated with FANFT, followed by diet with control tryptophan and vitamin B₆ levels (40%). The disease incidence was reduced in the vitamin B₆-deficient group (13%) and of an intermediate range in the groups fed a tryptophan excess with or without vitamin B₆ deficiency (28–29%). Tumors at other sites were greatest in number in FANFT-treated rats fed vitamin B₆-deficient diet with excess tryptophan and were significantly fewer in FANFT-treated rats fed vitamin B₆-deficient diet alone. Animals given diet deficient in vitamin B₆ consistently had depressed levels of alanine aminotransferase activity and plasma pyridoxyl phosphate. FANFT pretreatment decreased alanine aminotransferase activities in rats in some groups and the feeding of tryptophan had variable effects on alanine aminotransferase and plasma pyridoxyl phosphate levels. Urinary tryptophan metabolites were influenced by all treatments, but the results did not correlate with tumor yields. Urinary bladder ornithine decarboxylase activity was not altered in vitamin B₆-deficient female rats. These results do not support the hypothesis that increased dietary L-tryptophan promotes bladder carcinogenesis in rats, but other dietary factors might modify the process following FANFT initiation.

¹ Supported by Research Grants CA 33368 and CA 32513 and Laboratory Cancer Research Center Grant CA 36727 from the National Cancer Institute. Presented in part at the annual meeting of the Federation of American Societies for Experimental Biology, April 1984, St. Louis, MO (58) and at the annual meeting of the American Association for Cancer Research, May 1986, Los Angeles, CA (59).

² To whom requests for reprints should be addressed, at The Eppley Institute for Research in Cancer, University of Nebraska Medical Center, 42nd St. and Dewey Ave., Omaha, NE 68105-1065.

Received 6/19/86. Revised 11/13/86. Accepted 11/14/86.

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