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

The incidence of point mutations of H–, K– and N–ras and p53 oncogenes in male BALB/c mouse stomach tumors induced with A(r)–methyl–A(r)–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.