Rare Occurrence of ras and p53 Gene Mutations in Mouse Stomach Tumors Induced by N–Methyl–N–nitrosourea

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Abstract
The incidence of point mutations of H–, K– and N–ras and p53 oncogenes in male BALB/c mouse stomach tumors induced with Ar–methyl–Ar–nitrosourea (MNU) was examined by direct sequencing and PCR single–strand conformation polymorphism (PCR–SSCP). A mutation of GGT to AGT at K–ras codon 12 was found by SSCP in one adenocarcinoma from a total of 19 specimens including 5 adenocarcinomas, 9 adenomatous hypcrplastic regions, 1 squamous cell carcinoma and 4 normal–like stomach regions from 4 mice. No mutations were detected by direct sequencing of H–, K– and N–ras oncogenes at exons 1 (codons 12 and 13) and 2 (codon 61) in a total of 26 specimens comprising 10 adenocarcinomas, 10 adenomatons hyperplastic regions, 2 squamous cell carcinomas and 4 normal–like stomach regions from 6 mice. No mutations were detected by direct sequencing ofp53 oncogene at exons 5, 6, 7 and 8 in a total of 30 specimens including 13 adenocarcinomas, 8 adenomatous hyperplastic regions, 2 squamous cell carcinomas, 1 papilloma and 6 normal–like stomach regions from 7 mice. These results suggest that ras and p53 oncogenes do not play a role in mouse stomach carcinogenesis induced by MNU.

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