Effect of L-tryptophan excess and vitamin B6 deficiency on rat urinary bladder cancer promotion.
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.
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D003043:Cocarcinogenesis; D005200:FANFT; D008297:Male; D009955:Ornithine Decarboxylase / Q000652:urine; D011732:Pyridoxal Phosphate / Q000097:blood; D051381:Rats; D011916:Rats, Inbred F344; D012701:Serotonin / Q000652:urine; D014364:Tryptophan / Q000378:metabolism / Q000633:toxicity*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced*; D026681:Vitamin B 6 Deficiency / Q000150:complications* / Q000378:metabolism
D012701:Serotonin; D011732:Pyridoxal Phosphate; D005200:FANFT; D014364:Tryptophan; D000410:Alanine Transaminase; D009955:Ornithine Decarboxylase