Carcinogenesis, Vol 19, 855-860, Copyright © 1998 by Oxford University Press
S Yamamoto, M Tatematsu, M Yamamoto, H Fukami and S Fukushima
The histological background for multifocal and metachronous development of
urothelial carcinomas remains equivocal, although accumulated genetic
evidence suggests monoclonal origin of multiple urothelial carcinomas.
Clonal development of various preneoplastic and neoplastic urothelial
lesions of C3H<-->BALB/c chimeric mice induced by N-butyl-N-
(4-hydroxybutyl)nitrosamine (BBN) was immunohistochemically investigated
using a C3H strain-specific antibody. All tumor masses induced in the mice
treated with 0.05% BBN for 20 weeks were composed of neoplastic cells of a
single parental type, which is indicative of monoclonal lesions. Three of
10 animals harbored two or more separate carcinomas of different clonal
type, which is indicative of multicentric development applicable in this
model. Using DNAs derived from urothelial carcinomas and tumor-adjacent
urothelium of chimeric mice, polymerase chain reaction-single strand
conformation polymorphism (PCR-SSCP) analysis and direct sequencing were
performed for p53 gene exons 5-7. p53 mutations were identified in four of
11 (36%) dysplasias and non-invasive carcinomas (carcinoma in situ and pTa
tumor) and 13 of 22 (59%) invasive carcinomas. Only in a single case were
identical p53 mutations found in separate urinary bladder carcinomas. In
contrast to the random distribution of urothelial proliferating units in
chimeric mice without chemical supplement, invasive carcinomas in
BBN-treated mice were accompanied by widely-distributed preneoplastic and
neoplastic lesions of the same clonality, which occasionally had frequent
foci of microinvasion. This is indicative of lateral clonal expansion of
the clones, which precedes the bulk of invasive carcinomas. Thus, two
aspects of 'field change' of the urothelium became evident in this model:
either independent transformation events or lateral clonal expansion might,
respectively, result in multicentric and monoclonal carcinoma development
in the urinary tract.
ARTICLES
Clonal analysis of urothelial carcinomas in C3H/HeN<-->BALB/c chimeric mice treated with N-butyl-N-(4-hydroxybutyl)nitrosamine
First Department of Pathology, Osaka City University Medical School, Osaka, Japan.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Romanenko, A. Kakehashi, K. Morimura, H. Wanibuchi, M. Wei, A. Vozianov, and S. Fukushima Urinary bladder carcinogenesis induced by chronic exposure to persistent low-dose ionizing radiation after Chernobyl accident Carcinogenesis, November 1, 2009; 30(11): 1821 - 1831. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. D. Jones, M. Wang, J. N. Eble, G. T. MacLennan, A. Lopez-Beltran, S. Zhang, A. Cocco, and L. Cheng Molecular Evidence Supporting Field Effect in Urothelial Carcinogenesis Clin. Cancer Res., September 15, 2005; 11(18): 6512 - 6519. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Pantoja, L. de los Rios, A. Matheu, F. Antequera, and M. Serrano Inactivation of Imprinted Genes Induced by Cellular Stress and Tumorigenesis Cancer Res., January 1, 2005; 65(1): 26 - 33. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Yamamoto, A. Romanenko, M. Wei, C. Masuda, W. Zaparin, W. Vinnichenko, A. Vozianov, C. C. R. Lee, K. Morimura, H. Wanibuchi, et al. Specific p53 Gene Mutations in Urinary Bladder Epithelium after the Chernobyl Accident Cancer Res., August 1, 1999; 59(15): 3606 - 3609. [Abstract] [Full Text] [PDF]
|
|