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© 1994 Oxford University Press

other

p53 mutations in early neoplastic lesions of the urinary bladder in rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine

Tsuneo Masui 2, Ihmin Don 1, Nobuyasu Takada 1, Kumiko Ogawa, Tomoyuki Shirai and Shoji Fukushima 1 3

First Department of Pathology, Nagoya City University Medical School Kawasumi, Mizuho-ku, Nagoya 467
1First Department of Pathology Osaka City University Medical School, Asahi-machi, Abeno-ku, Osaka 545, Japan

3To whom correspondence should be addressed

Rat experimental models using Ar-butyl-Af-(4-hydroxybutyl) nitrosamine (BBN) as an initiating agent have been widely used to study carcinogenic processes in the urinary bladder. In this study, early neoplastic lesions from 10 male F344 rats treated with 0.05% BBN for 16 weeks were analyzed for changes in the H-ras or p53 genes by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis and subsequent DNA sequencing. Lesions were pooled for each of the 10 rats and six showed point mutations in the p53 gene and one in the H-ras gene. These results would indicate that BBNinduced rat urinary bladder carcinomas are similar to human urinary bladder carcinomas with respect to alterations in the p53 and H-ras genes and that p53 gene alterations are relatively early events in rat urinary bladder carcinogenesis induced by BBN treatment


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