Carcinogenesis, Vol 18, 1877-1882, Copyright © 1997 by Oxford University Press
S Yamamoto, T Chen, T Murai, S Mori, K Morimura, T Oohara, S Makino, M Tatematsu, H Wanibuchi and S Fukushima
In a variety of human malignancies, alteration of the p53 tumour suppressor
gene is known as a significant indicator of late progression events
including invasion and metastasis, with a possible close relationship to
genetic instability. Mutational analysis of the p53 and H-ras genes was
performed for 10 pairs of N-butyl-N-(4- hydroxybutyl)nitrosamine-induced
invasive mouse urinary bladder carcinomas and metastatic foci. p53
Mutations were found in nine of 10 (90%) primary carcinomas and seven of 10
(70%) metastatic foci. A total of eight p53 mutations in primary carcinomas
were common in metastatic foci in six pairs. Additional p53 or H-ras
mutations which were not identified in the primary carcinomas were found in
three metastatic foci. Evaluation of the allelic distribution of the p53
mutations using RT-PCR, PCR and subcloning, further indicated possible
intra-tumour genomic heterogeneity or excess copy numbers of the p53 gene
due to genetic instability. Overall, p53 alterations were frequent in mouse
urinary bladder carcinomas demonstrating progression. The results suggest
that genetic instability might underlie generation of additional genetic
alterations in this animal model.
ARTICLES
Genetic instability and p53 mutations in metastatic foci of mouse urinary bladder carcinomas induced by N-butyl-N-(4- hydroxybutyl)nitrosamine
First Department of Pathology, Osaka City University Medical School, Osaka, Japan.
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