Cocarcinogenic interaction between D,L-tryptophan and 4-aminobiphenyl or 2-naphthylamine in dogs

Administration of a dietary supplement of 6 g D,L tryptophan/day for 4 1/2 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.