Loss of chromosome 14 increases the radiosensitivity of CGL1 human hybrid cells but lowers their susceptibility to radiation-induced neoplastic transformation

Loss of active tumor suppressor alleles on fibroblast chromosomes 11 and 14 are involved in radiation-induced neoplastic transformation of human hybri d CGL1 cells. Loss of either chromosome 11 or 14 alone is not sufficient fo r neoplastic transformation. To gain insight into the potential functions o f these tumor suppressor loci, we have investigated the effects of chromoso me 11 or 14 loss on radiation-induced neoplastic transformation. We recentl y demonstrated that loss of chromosome 11 increases the susceptibility to X -ray induced cell killing, neoplastic transformation and the expression of delayed death. The data suggested that one possible function of the chromos ome 11 tumor suppressor gene may be to help maintain genome stability after radiation damage. We postulated that if the chromosome 14 allele is functi oning in a similar manner, then the loss of chromosome 14 may also make the hybrid cells more susceptible to radiation-induced cell killing and neopla stic transformation. A hybrid cell line which has lost one copy of chromoso me 14 was isolated and designated CON3(-14), CON3(-14) cells were more sens itive to X-ray-induced cell killing when compared with parental CGL1 cells. However, the susceptibility to radiation-induced neoplastic transformation was significantly reduced (by a factor of two) compared with the parental CGL1 cells. The expression of delayed death in the progeny of the irradiate d CON3(-14) cells, growing in transformation flasks, was similar to CGL1 ce lls during the 21 day assay period. Taken together, the data indicate that loss of chromosome 14 alone increased the X-ray sensitivity of the hybrid c ells but reduced their susceptibility to radiation-induced neoplastic trans formation, These data suggest that the tumor suppressor alleles on chromoso mes 11 and 14 may be functionally distinct in terms of their regulation of genomic instability and neoplastic transformation after radiation exposure.