Clonal chromosomal aberrations in simian virus 40-transfected human thyroid cells and in derived tumors developed after in vitro irradiation.
In vitro model cell systems are important tools for studying mechanisms of radiation-induced neoplastic transformation of human epithelial cells. In our study, the human thyroid epithelial cell line HTori-3 was analyzed cytogenetically following exposure to different doses of alpha- and gamma-irradiation and subsequent tumor formation in athymic nude mice. Combining results from G-banding, comparative genomic hybridization, and spectral karyotyping, chromosome abnormalities could be depicted in the parental line HTori-3 and in nine different HTori lines established from the developed tumors. A number of chromosomal aberrations were found to be characteristic for simian virus 40 immortalization and/or radiation-induced transformation of human thyroid epithelial cells. Common chromosomal changes in cell lines originating from different irradiation experiments were loss of 8q23 and 13cen-q21 as well as gain of 1q32-qter and 2q11.2-q14.1. By comparison of chromosomal aberrations in cell lines exhibiting a different tumorigenic behavior, cytogenetic markers important for the tumorigenic process were studied. It appeared that deletions on chromosomes 9q32-q34 and 7q21-q31 as well as an increased copy number of chromosome 20 were important for the tumorigenic phenotype. A comparative breakpoint analysis of the marker chromosomes found and those observed in radiation-induced childhood thyroid tumors from Belarus revealed a coincidence for a number of chromosome bands. Thus, the data support the usefulness of the established cell system as an in vitro model to study important steps during radiation-induced malignant transformation in human thyroid cells.
Zitzelsberger
H
H
Institute of Radiobiology, GSF-Forschungszentrum für Umwelt und Gesundheit GmbH, Neuherberg, Germany. Zitzelsberger@gsf.de
Bruch
J
J
Smida
J
J
Hieber
L
L
Peddie
C M
CM
Bryant
P E
PE
Riches
A C
AC
Fung
J
J
Weier
H U
HU
Bauchinger
M
M
D000818:Animals; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D002869:Chromosome Aberrations; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009381:Neoplasms, Radiation-Induced / Q000473:pathology / Q000821:virology; D013539:Simian virus 40; D013961:Thyroid Gland / Q000473:pathology* / Q000528:radiation effects / Q000821:virology*; D013964:Thyroid Neoplasms / Q000209:etiology* / Q000235:genetics / Q000473:pathology* / Q000821:virology; D014162:Transfection