Selective mutation of codons 204 and 213 of the p53 gene in rat tumors induced by alkylating N-nitroso compounds.
Kidney and esophageal tumors induced by alkylating N-nitroso compounds 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 first base of codon 204 and the second base of 213, leading to amino acid substitutions Glu----Lys and Arg----Gln, 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 N-nitrosoethylurea and 56% of esophageal tumors induced by N-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 epidemiological studies on this class of chemical carcinogens.
Ohgaki
H
H
Institute of Neuropathology, University of Zürich, Switzerland.
Hard
G C
GC
Hirota
N
N
Maekawa
A
A
Takahashi
M
M
Kleihues
P
P
D000215:Acylation; D000483:Alleles; D000818:Animals; D001483:Base Sequence; D003062:Codon / Q000235:genetics*; D005091:Exons / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics*; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics*; D009603:Nitroso Compounds; D051381:Rats; D011919:Rats, Inbred Strains; D009396:Wilms Tumor / Q000139:chemically induced / Q000235:genetics
D003062:Codon; D009603:Nitroso Compounds