Long-term treatment with l-isoleucine or l-leucine in AIN-93G diet has promoting effects on rat bladder carcinogenesis

In the present study, effects of l-leucine and l-isoleucine on rat bladder carcinogenesis were investigated using AIN-93G and MF basal diet. In Experiment 1, N-butyl-N-(4-hydroxybutyl)-nitrosamine was used as an initiator of bladder carcinogenesis. In the AIN-93G diet groups, a significantly higher incidence and multiplicity of bladder tumors, accompanied by decreased final body weight, was observed in the l-leucine-supplemented group and a significantly higher incidence of papillomas and total tumors was observed in the l-isoleucine-supplemented group. In the MF diet groups, the multiplicity of papillary and nodular hyperplasia was significantly increased in the l-isoleucine-supplemented group. Urinary pH values were not affected by supplementing either type of diet with l-leucine or l-isoleucine. In Experiment 2, the amino acid was administered in the basal diets for 2 weeks without initiator. No pathological lesions were observed in the bladder urothelium in any of the groups, and no significant differences in urinary pH values, microcrystals or aggregates were observed between the amino acid-supplemented groups and their respective control groups. In conclusion, long-term treatment with l-leucine or l-isoleucine has a promoting effect on rat bladder carcinogenesis; therefore, their long-term use as a dietary supplement for bladder cancer patients should be avoided until more is known.