Previous loss of chromosome 11 containing a suppressor locus increases radiosensitivity, neoplastic transformation frequency and delayed death in HeLa x fibroblast human hybrid cells.
CGL1 (HeLa x fibroblast) hybrid cells have been utilized to study mechanisms of radiation-induced neoplastic transformation of human cells in vitro. Previous analysis has shown that loss of active tumor suppressor alleles on fibroblast chromosomes 11 and 14 may be required for radiation-induced neoplastic transformation of CGL1 cells. Loss of chromosome 11 alone was, therefore, found to be necessary but not sufficient for neoplastic transformation. We postulated that the loss of chromosome 11 may make the hybrid cells more susceptible to radiation-induced neoplastic transformation, since these cells have already undergone one of the required tumor suppressor loss events. Hybrid cells which have lost one copy of chromosome 11 were designated CON104(-11). CON104(-11) hybrid cells were found to have increased X-ray sensitivity and susceptibility to radiation-induced neoplastic transformation when compared with the parental CGL1 cells. In addition, the neoplastically transformed foci appear to arise earlier after radiation exposure in CON104(-11) versus CGL1 cells. Furthermore, the plating efficiency (PE) of the progeny of the irradiated CON104(-11) cells, growing in transformation flasks, is persistently lower than parental CGL1 cells during the 21 day assay period. The lower PE of the progeny of irradiated cells was attributed to the expression of delayed death/lethal mutations post-irradiation, a reflection of genomic instability. Taken together, the data indicate that previous loss of chromosome 11 may increase the radiation-induced genomic instability of the hybrid cells, leading to increased radiation sensitivity and neoplastic transformation potential. The data suggest that one possible function of the chromosome 11 tumor suppressor gene may be to help maintain genome stability after radiation damage.
Mendonca
M S
MS
Radiation and Cancer Biology Laboratory, Department of Radiation Oncology, 975 West Walnut Street, IB-346, Indiana University School of Medicine, Indianapolis, IN 46202, USA. mmendonc@iupi.edu
Howard
K
K
Desmond
L A
LA
Derrow
C W
CW
D016923:Cell Death / Q000528:radiation effects; D002455:Cell Division / Q000528:radiation effects; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000528:radiation effects*; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D006822:Hybrid Cells; D013997:Time Factors; D014410:Tumor Stem Cell Assay; D014965:X-Rays