Roles of Leucine and Isoleucine in Experimental Models of Bladder Carcinogenesis

There are increasing concerns about the influence of branched chain amino acid (BCAA) supplementation on the risk of cancer. However, there is no epidemiological data relevant to an association of dietary BCAA and the risk of cancer. Ex perimental studies evaluating the effects of leucine and isoleucine on urinary bladder carcinogenesis using a two-stage (initiation-promotion) carcinogenesis protocol with male F344 rats found that supplementation of CE2 and AIN-93G di -ets, but not an MF diet, with leucine or isoleucine has tumor-promoting activity on bladder carcinogenesis in rats. These findings indicate that the effects of dietary leucine and isoleucine on rat bladder carcinogenesis are dependent on the type of basal diet used. Importantly, leucine and isoleucine increased expression of amino acid transporters in bladder carcinogen-initiated urothelial cells; but in hyperplasias and bladder tumors, increased expression of these transporters became independent of leucine and isoleucine. Furthermore, leucine or isoleucine themselves do not induce toxicity; therefore, regenerative proliferation is not likely to be involved in their tumor - promoting activity. Leucine and isoleucine are essential amino acids that cannot be synthesized in the body, making optimum intake of these BCAAs essential for health. However, given the results of the above animal experiments, the long-term use of unnecessarily high dose of leucine and isoleucine should be avoided until more is known about their effects on carcinogenesis; this is particularly applicable to patients with bladder cancer. ferences in pH values between the amino acid-supplemented groups and the basal diet control groups. Analysis of urine sediment by scanning electron microscopy (SEM) showed that several kinds of urine microcrystals and aggregates were present in the MF diet groups, however, no significant differences were observed between the amino acid supplemented groups and the basal diet control groups. In the AIN-93G diet groups, there were no obvious urine sediments. These results suggest that the promoting effect of leucine or isoleucine in the AIN-93G diet groups is not related to urinary pH or formation of urine sediments. Importantly, no pathological lesions were observed in the bladder urothelium by light microscope or SEM in any of the groups. In addition, there were no treatment-related alterations in the kidneys in any of the groups. These findings indicate that these two amino acids themselves do not induce toxicity; therefore, regenerative proliferation is not likely to be involved in their tumor promoting activity in the urinary bladder.