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Urinary bladder cardnogenesis induced by melamine in F344 male rats.pdf

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Urinary bladder cardnogenesis induced by melamine in F344 male rats

Carclnogenesis vol.16 no. 11 pp.2773-2777, 1995 Urinary bladder cardnogenesis induced by melamine in F344 male rats: correlation between carcinogenicity and urolith formation Hiroyuki Ogasawara, Katsumi Imaida 1 , Hajimu Ishiwata 2 , Kazuhiro Toyoda, Tom Kawanishi, Chikako Uneyama, Shuji Hayashi, Michihito TakahashP and Yuzo Hayashi Division of Pathology and 2 Food Additives, National Institute of Health Sciences, Kamiyoga 1-18-1, Setagaya-ku, Tokyo 158, and Department of Pathology, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 457, Japan ^To whom correspondence should be addressed Urinary bladder carcinogenesis associated with melamine treatment was examined with concomitant use of NaCl to allow assessment of the relationship between uroliths and lesion development Analysis of the chemical composition of calculi was also performed. F344/DuCrj male rats received diets containing 3 or 1% melamine alone or in combination with either 10 or 5% NaCl, or 10% NaCl alone for 36 weeks, and then diet without NaCl supplement for a further 4 weeks. The water intake, used as an index of urinary output, was increased by NaCl treatment The incidences of bladder transitional cell carcinomas and papillomas were 90 and 55% in the group treated with 3% melamine alone; 0 and 15% in the group treated with 3% melamine and 10% NaCl; 21 and 42% in the group treated with 1% melamine alone; and zero in the other groups. Calculus formation resulting from melamine administra- tion was suppressed dose-dependently by the simultaneous NaCl treatment, along with the occurrence of hyperplasia of the papilla in the kidneys. The main constituent of calculi were melamine itself and uric acid (total contents 61.1-81.2%), contained in equal molar ratio. The results indicate that melamine-induced proliferative lesions of the urinary tract of rats were directly due to the irritative stimulation of calculi, and not molecular interactions between melamine itself or its me