Selective Mutation of Codons 204 and 213 of the p53 Gene in Rat Tumors Induced by Alkylating W-Nitroso Compounds'

Kidney and esophageal tumors induced by alkylating /V-nitroso com pounds in rats contain a high incidence (75-100%) of G -> A transition mutations in the p53 gene. These are almost selectively (89%) located in the tirsi base of codon 204 and the second base of 213, leading to amino acid substitutions Glu -»Lys and Arg -»Gin, respectively. In contrast to human neoplasms, a considerable fraction of rat kidney and esophageal tumors carries multiple p53 mutations. All nephroblastomas induced by transplacental exposure to /V-nitrosoethylurea and 56% of esophageal tumors induced by /V-nitrosomethylurea showed double mutations in codons 204 and 213 of exon 6. The selective targeting of p53 codons by alkylating nitrosamines may provide a basis for molecular epidemiolÃ3gi ca! studies on this class of chemical carcinogens.