Rat p53 gene mutations in primary Zymbal gland tumors induced by 2-amino-3-methylimidazo[4,5-f]quinoline, a food mutagen.
There are reports of p53 gene mutations in various human cancers but not in rat tumor cell lines or rat primary tumor tissue. We found a p53 gene mutation in a cell line of a spontaneous squamous cell carcinoma of the rat Zymbal gland, SCC131, at codon 171 by direct sequencing of cDNA fragments amplified by PCR. We tested for p53 gene mutations in 15 primary Zymbal gland tumors induced by 2-amino-3-methylimidazo[4,5-f]quinoline by single-strand conformation polymorphism analysis of the PCR-amplified cDNA products. Samples of four tumors showed mobility shifts. Direct sequencing revealed that all these tumors had mutations in conserved regions or in scattered conserved residues. Single-strand conformation polymorphism analysis of cDNA suggested that mRNA from the wild-type allele of the p53 gene was not present in tumor cells of three of four positive cases, although genomic DNA analysis indicated that the wild-type allele was retained in all the cases. All mutations were found at a guanine base: three mutations were guanine----pyrimidine transversions and one was a deletion of a guanine base within a G+C-rich sequence. These findings indicate that 2-amino-3-methylimidazo[4,5-f]quinoline may be directly involved in induction of these mutations by forming DNA adducts at various sites in the p53 gene.
Makino
H
H
Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, Japan.
Ishizaka
Y
Y
Tsujimoto
A
A
Nakamura
T
T
Onda
M
M
Sugimura
T
T
Nagao
M
M
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics*; D016158:Genes, p53; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009154:Mutation; D009374:Neoplasms, Experimental / Q000235:genetics*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011804:Quinolines / Q000633:toxicity*; D051381:Rats; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D004273:DNA, Neoplasm; D009838:Oligodeoxyribonucleotides; D011804:Quinolines; D016159:Tumor Suppressor Protein p53; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D004247:DNA