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© 1992 Oxford University Press

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Relationship between calculus formation and carcinogenesis in the urinary bladder of rats administered the non-genotoxic agents, thymine or melamine

Masanao Okumura 1 2, Ryohei Hasegawa 1, Tomoyuki Shirai 1, Masao Ito 2, Seiji Yamada 2 and Shoji Fukushima 1 3

1First Department of Pathology, Nagoya City University Medical School, I Kawasumi Mizuho-cho, Mizuho-ku, Nagoya 467
2Laboratory of Biology, Aichi Prefectural Institute of Public Health 7-6 Nagare, Tsuji-machi, Kita-ku. Nagoya 462, Japan
3Present address: First Department of Pathology, Osaka City University Medical School 1-4-54 Asahi-machi, Abeno-ku, Osaka 545, Japan

Urinary bladder lesions induced by administration of thymine or melamine were investigated in male F344 rats. Animals, 6 weeks old at the beginning of the experiment, received either 3.0 or 1.0% thymine or 3.0, 1.0 or 0.3% melamlne in the diet for 36 weeks followed by a 4 week period without chemicals, the total observation time being 40 weeks. Carcinomas of the urinary bladder were observed in 1/20 (5%) rats in each of the 3.0% thymine and 1.0% melamine groups, and in 15/19 (79%) animals given the 3.0% melamine treatment. Papillomas were induced in 9/20(45%), 12/19(63%) and 1/20 (5%) among rats receiving the 3.0% thymine, 3.0% and 1.0% melamine treatments respectively. Exploratory laparotomy at the end of week 36 revealed calculus formation in 9/10 (90%), 10/10(100%) and 7/10(70%) rats in these groups. In the ureter of the 3.0% melamine treated group, a carcinoma and papillomas were induced in 1/19 (5%) and 3/19 (16%) animals respectively. However, no tumors were observed in the renal pelvis in any of the other treated groups. Thus, administration of 3.0% thymine in the diet results in calculus formation in the urinary bladder of F344 rats, and is associated with development of tumors. It was also confirmed that a 3.0% dose level of melamine in the diet induces tumors in both the urinary bladder and the ureter.


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