In vitro radiation-induced neoplastic progression of low-grade uroepithelial tumors.
Recent interest has focused on the identification of molecular genetic mechanisms in multistep neoplastic transformation. In vitro exposure of simian virus 40 (SV40)-immortalized human uroepithelial cells (SV-HUC) that are environmentally relevant to bladder carcinogens has been shown to produce tumorigenic transformation, as assessed by the ability of cells exposed to a carcinogen to form xenograph tumors with heterogeneous cancer phenotypes ranging from very aggressive, invasive high-grade carcinomas to superficial low-grade indolent tumors. In addition, exposure of a low-grade indolent tumor generated in the SV-HUC system, MC-T11, to the same carcinogens results in neoplastic progression as assessed by the production of high-grade aggressive cancers. In the present study, we show neoplastic progression of MC-T11 after in vitro exposure to a single dose of 6 Gy X rays. In addition, we show that the chromosome deletions, including losses of 4q, 11p, 13q and 18, observed in these radiation-induced tumors are similar to those observed in carcinogen-induced tumors, thus supporting the hypothesis that the experimental cell system, not the transforming agent, dictates the genetic losses required for tumorigenic transformation and progression.
Pazzaglia
S
S
Department of Human Oncology, University of Wisconsin, Madison 53792.
Chen
X R
XR
Aamodt
C B
CB
Wu
S Q
SQ
Kao
C
C
Gilchrist
K W
KW
Oyasu
R
R
Reznikoff
C A
CA
Ritter
M A
MA
D000818:Animals; D002455:Cell Division / Q000528:radiation effects; D002460:Cell Line; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000528:radiation effects*; D002872:Chromosome Deletion; D002877:Chromosomes, Human / Q000528:radiation effects*; D002880:Chromosomes, Human, Pair 11 / Q000528:radiation effects; D002882:Chromosomes, Human, Pair 13 / Q000528:radiation effects; D002887:Chromosomes, Human, Pair 18 / Q000528:radiation effects; D002894:Chromosomes, Human, Pair 4 / Q000528:radiation effects; D004848:Epithelium / Q000528:radiation effects; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D007700:Kinetics; D051379:Mice; D008819:Mice, Nude; D013539:Simian virus 40 / Q000235:genetics; D013997:Time Factors; D014162:Transfection; D014183:Transplantation, Heterologous; D001743:Urinary Bladder / Q000166:cytology / Q000528:radiation effects; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology*; D014965:X-Rays