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Incidence of p53 and Ha‐ras gene mutations in chemically induced rat mammary carcinomas
Author(s) -
Kito Katsumi,
Kihana Toshimasa,
Sugita Atsuro,
Murao Shinichi,
Akehi Shun,
Sato Motomichi,
Tachibana Mari,
Kimura Shigeru,
Ueda Norifumi
Publication year - 1996
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/(sici)1098-2744(199610)17:2<78::aid-mc4>3.0.co;2-p
Subject(s) - biology , gene , cancer research , incidence (geometry) , mutation , genetics , microbiology and biotechnology , physics , optics
To determine whether p53 alterations, which are frequent in human breast cancers, are also common in rat mammary tumors, we examined 40 tumors from 24 rats treated with 7,12‐dimethylbenz[a]anthracene (DMBA) and 34 tumors from 14 rats treated with N ‐nitroso‐ N ‐methylurea (NMU) (an N‐nitroso compound). DMBA and NMU are known genotoxic mutagens. The entire coding regions of the p53 and Ha‐ ras genes were examined for mutations by polymerase chain reaction single‐strand conformational polymorphism analysis and by direct sequencing. One of the 40 DMBA‐induced mammary tumors had a p53 mutation, a single‐base substitution (???AGC→???GGC) at codon 307, resulting in an amino‐acid change from Ser to Gly. No mutations were found in NMU‐induced tumors. The incidence of Ha‐ ras gene mutation was 79% (27 of 34) at codon 12 in the NMU group and 23% (nine of 40) at codon 61 in the DMBA group. Thus, p53 mutation, in contrast to Ha‐ ras mutation, did not seem to be a prerequisite for carcinogenesis in chemically induced rat mammary tumors. © 1996 Wiley‐Liss, Inc.