Detection of a Ha- ras point mutation by polymerase chain reaction-single strand conformation polymorphism analysis in 2-amino-3,4-dimethylimidazo[4,5- f]quinoline-induced mouse forestomach tumors

Abstract

Ha-ras activation in forestomach squamous cell carcinomas of CDF 1 mice induced by 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), one of the heterocyclic amines isolated from broiled sardine was analyzed. Mutations were detected in two of three primary original carcinomas and two of four cell lines derived from other independent carcinomas by the polymerase chain reaction followed by analysis of single strand conformation polypolymorphism and direct sequencing. All the mutations detected were G → T transversions at the second letter of codon 13 resulting in an amino acid change from Gly to Val. This finding together with the previous reports on squamous cell carcinomas of the rat Zymbal gland suggest that MeIQ induces a specific type of mutation at a specific site of the Ha-ras gene during squamous cell carcinogenesis, in a species-independent manner.