The effects of saccharin on the metabolism of dietary tryptophan to indole, a known cocarcinogen for the urinary bladder of the rat.
Adult male rats were fed diets containing 0 to 10% saccharin, 2% tryptophan, or 2% tryptophan plus 5% saccharin ad libitum for 1 to 2 months. Saccharin produced a dose-related increase in the urinary excretion of indican which is the main metabolite of indole. The renal clearances of both indican and saccharin were reduced at high plasma concentrations (200 to 300 micrograms/ml) of saccharin, suggesting saturation of renal tubular secretion. The increased amounts of indican in the urine, and of indole in the cecum arose from accumulation of protein and tryptophan in the cecum rather than an increase in the enzyme tryptophanase which metabolizes tryptophan to indole. The high levels of protein in the ceca of rats fed saccharin-containing diets were associated with a dose-related increase in the weight of the contents and wall of the cecum. Administration of 2% tryptophan in the diet increased significantly the amounts of tryptophan in the cecum and in plasma, but produced only small increases in the size of the cecum, the amount of indole present, and the excretion of indican. The effects of saccharin and tryptophan were additive. These effects are consistent with saccharin having a major effect on protein digestion in the intestine such that increased amounts of tryptophan are available in the cecum for microbial metabolism to indole. The greater formation of indole and excretion of indican in the urine suggest that saccharin increases the catabolism of dietary tryptophan to metabolites with known cocarcinogenic activity toward the rat bladder.
D000818:Animals; D002432:Cecum / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005243:Feces / Q000382:microbiology; D007200:Indican / Q000378:metabolism*; D007422:Intestines / Q000201:enzymology; D008297:Male; D009374:Neoplasms, Experimental / Q000139:chemically induced; D009601:Nitroreductases; D009929:Organ Size / Q000187:drug effects; D010088:Oxidoreductases / Q000032:analysis; D010434:Pepsin A / Q000037:antagonists & inhibitors; D011506:Proteins / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D012439:Saccharin / Q000633:toxicity*; D014364:Tryptophan / Q000378:metabolism*; D014368:Tryptophanase / Q000032:analysis; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced*
D011506:Proteins; D014364:Tryptophan; D010088:Oxidoreductases; D009601:Nitroreductases; D010434:Pepsin A; D014368:Tryptophanase; D012439:Saccharin; D007200:Indican