Fermented brown rice by Aspergillus oryzae (FBRA) has been shown to be a potent anti-carcinogenic compound. Here, we investigated the modifying effects of dietary feeding with a naturally occurring anti-oxidant FBRA on N-butyl-N-(4-hydroxybutyl)-nitrosamine (OH-BBN)-induced urinary bladder carcinogenesis in male ICR mice. Five-week-old male ICR mice were divided into 7 groups, and groups 1-5 were given OH-BBN (500 ppm) in drinking water for 6 weeks starting at 7 weeks of age. Groups 2 and 3 were fed the diet containing 5% and 10% FBRA during the initiation phase, respectively, whereas groups 4 and 5 were fed these diets during the post-initiation phase. Group 6 was given the diet containing 10% FBRA throughout the experiment, and group 7 was kept on the basal diet alone and served as an untreated control. At the end of the study (week 32), the incidences of simple hyperplasia, dysplasia and carcinoma in the bladders of group 1 (OH-BBN alone) were 92%, 49% and 38%, respectively. Those of group 5 (64%, 23% and 10%) and the incidence of carcinoma of group 4 (17%) was significantly less than that of group 1. Furthermore, the multiplicity of simple hyperplasia and carcinoma of group 5 was significantly less than that of group 1. Post-initiation exposure of 10% FBRA significantly decreased the number/nucleus of silver-stained nucleolar organizer region proteins (AgNORs), an index of cell proliferation, in the non-lesional transitional epithelium when compared to that of the control. Our results indicate that FBRA exerts chemopreventive effects against chemically induced urinary bladder carcinogenesis through anti-proliferative mechanisms. FBRA could be a promising chemopreventive agent for human urinary bladder cancer.

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