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 o ur study, the human thyroid epithelial cell line HTori-3 was analyzed cytog enetically following exposure to different doses of alpha- and gamma -irrad iation and subsequent tumor formation in at athymic nude mice. Combining re sults from G-banding, comparative genomic hybridization, and spectral karyo typing, chromosome abnormalities could be depicted in the parental line HTo ri-3 and in nine different HTori lines established from the developed tumor s. 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 or iginating from different irradiation experiments were loss of 8q23 and 13ce n-q21 as well as gain of 1q32-qter and 2q11.2-q14.1. By comparison of chrom osomal aberrations in cell lines exhibiting a different tumorigenic behavio r, cytogenetic markers important for the tumorigenic process were studied. It appeared that deletions on chromosomes 9q32-q34 and 7q21-q31 as cs ell a s an increased copy number of chromosome 20 were important for the tumorige nic 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 transform ation in human thyroid cells. (C) 2001 Wiley-Liss, Inc.