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Mutation, loss of heterozygosity, and recombination of the p53 gene in mouse forestomach tumors induced by 2‐amino‐3,4‐dimethylimidazo[4,5‐ f ]quinoline
Author(s) -
Ushijima Toshikazu,
Makino Hiroshi,
Okonogi Hideo,
Hosoya Yoko,
Sugimura Takashi,
Nagao Minako
Publication year - 1995
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.2940120105
Subject(s) - biology , transversion , loss of heterozygosity , single strand conformation polymorphism , microbiology and biotechnology , carcinogenesis , point mutation , gene , exon , mutagen , genetics , mutation , allele , cancer research , dna
2‐Amino‐3,4‐dimethylimidazo[4,5‐ f ]quinoline (MelQ), a food mutagen, induces forestomach tumors in CDF 1 mice. We established a polymerase chain reaction (PCR)–single‐strand conformation polymorphism (SSCP) analysis system to detect mutations in the mouse p53 gene exons 2–10, which encompass all five regions conserved among species, and a system to examine loss of heterozygosity (LOH) that uses newly identified polymorphisms between BALB/c and DBA mice, the parental strains of CDF 1 mice. Four original forestomach tumors (one papilloma, two carcinomas, and one lymph‐node metastasis) and four cell lines derived from four independent forestomach tumors were examined with the PCR‐SSCP system and by polymorphism analysis. Of the four original tumors, the papilloma had a G→A transition at the second position of codon 171, and one carcinoma had a G→T transversion at the second position of condon 113 with loss of the wild‐type allele, whereas the other two carcinomas had no detectable mutations. Of the four cell lines, two had a base substitution and LOH, and the other two had double mutations (a base substitution and a deletion). By amplification of the double mutations in a fragment, the two cell lines were shown to have four kinds of alleles, indicating induction of recombination within the p53 gene. Our results show that our PCR‐SSCP analysis system is efficient for detecting p53 mutations in mouse genomic DNA and that alteration of the p53 gene plays a significant role in MelQ‐induced mouse forestomach carcinogenesis. © 1995 Wiley‐Liss Inc.