Premium
Infrequent mutation of ha‐ras and p53 in rat mammary carcinomas induced by 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐ b ]pyridine
Author(s) -
Ushijima Toshikazu,
Kakiuchi Hideki,
Makino Hiroshi,
Hasegawa Ryohei,
Ishizaka Yukihito,
Hirai Hisamaru,
Yazaki Yoshio,
Ito Nobuyuki,
Sugimura Takashi,
Nagao Minako
Publication year - 1994
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.2940100107
Subject(s) - biology , carcinogenesis , mutation , microbiology and biotechnology , single strand conformation polymorphism , carcinogen , gene , point mutation , amino acid , complementary dna , biochemistry
2‐Amino‐1‐methyl‐6‐phenylimidazo[4,5‐ b ]pyridine(PhlP) is the most abundant of the heterocyclic amines, a group of potent carcinogens contained in cooked meat and fish. Female F344 rats fed a diet containing 100 or 400 ppm PhIP developed mammary carcinomas within 104 or 52 wk, respectively, at the rate of 47% for each group; these carcinomas were examined for mutations in three members of the ras gene family and in the p53 gene. Single‐strand conformation polymorphism (SSCP) analysis and direct sequencing demonstrated a G←A transition at the second position of Ha‐ ras codon 12, with the resultant substitution of glutamic acid for glycine, in two of 10 carcinomas induced by 100 ppm PhIP and in one of seven induced by the 400 ppm dose. No mutations in Ki‐ ras or N‐ ras were detected. cDNA polymerase chain reaction‐SSCP analysis and direct sequencing demonstrated a G←Ttransversion at the third position of p53 codon 130, with the resultant substitution of asparagine for lysine, in one of the 10 carcinomas induced by 100 ppm of PhIP for which freshly frozen samples were available. PhlP‐induced rat mammary carcinogenesis can be regarded as a unique system in that rat mammary carcinomas are negative for ras and p53 mutations. © 1994 Wiley‐Liss, Inc.