Cocarcinogenic Interaction Between d,l-Tryptophan and 4-Aminobiphenyl or 2-Naphthylamine in Dogs

• Published in: JNCI : Journal of the National Cancer Institute 1977-06, Vol.58 (6), p.1831-1834
• Main Authors: Radomski, Jack L., Radomski, Teresa, MacDonald, William E.
• Format: Article
• Language: English
• Subjects: 2-Naphthylamine - administration & dosage; 2-Naphthylamine - toxicity; Aminobiphenyl Compounds - administration & dosage; Aminobiphenyl Compounds - toxicity; Animals; Carcinogens; Dogs; Drug Administration Schedule; Drug Interactions; Female; Naphthalenes - toxicity; Neoplasms, Experimental - chemically induced; Tryptophan - administration & dosage; Tryptophan - toxicity; Urinary Bladder Neoplasms - chemically induced
• ISSN: 0027-8874; 1460-2105
• DOI: 10.1093/jnci/58.6.1831

Administration of a dietary supplement of 6 g d,ltryptophan/day for 4½ years following the administration of a single dose of 50 mg 4-aminobiphenyl/kg produced a bladder tumor in 1 of 4 beagle dogs. No tumors were observed in 6 dogs given the same dose of 4-aminobiphenyl without supplemental tryptophan. In a second experiment, administration of a supplement of 6 g d,l-tryptophan/day for 3 years following the administration of 5 mg 2-naphthylamine/kg/day for 30 days produced bladder tumors in 2 of 4 dogs. No tumors or other bladder pathology was produced by treatment of 4 dogs with this dose of 2-naphthylamine alone. Dogs given d,l-tryptophan alone developed no bladder tumors, but in most dogs receiving tryptophan the “tryptophan effect,” i.e., a darkly stained mucosa with white areas of focal hyperplasia, was observed. Both experiments suggest a role of d,l-tryptophan as a cocarcinogen or promotor in the induction of bladder cancer.