LOSS OF SUPPRESSOR LOCI ON CHROMOSOME-11 AND CHROMOSOME-14 MAY BE REQUIRED FOR RADIATION-INDUCED NEOPLASTIC TRANSFORMATION OF HELA X SKIN FIBROBLAST HUMAN CELL HYBRIDS

We have previously reported a linkage between radiation-induced damage to a putative tumor suppresser locus on fibroblast chromosome 11 and the re-expression of tumorigenicity in a hybrid cell line (HeLa x huma n skin fibroblast) used to study neoplastic transformation. Further in vestigation into the molecular basis of radiation-induced neoplastic t ransformation of the hybrid cell, CGL1, indicates that loss of fibrobl ast chromosome 11 appears to be necessary but not sufficient for neopl astic transformation. Previous analysis had suggested, though not clea rly demonstrated, a possible role for loss of alleles on fibroblast ch romosome 14 in the neoplastic transformation of the hybrid cells. Ther efore, the status of chromosome 14 in the gamma-ray-induced, neoplasti cally transformed (GIM) hybrid cell lines and in nontumorigenic contro l (CON) hybrid cell lines isolated from irradiated populations has bee n investigated. Chromosome painting and molecular studies using restri ction fragment length polymorphisms and tetranucleotide repeat polymor phism analysis were performed. As an additional control, the status of chromosome 12 was also examined. We report that five of the eight GIM cell lines have lost one complete copy of a fibroblast chromosome 14 while only one of the five CON cell lines has lost a complete copy of a fibroblast chromosome 14. No evidence of large-scale loss of chromos ome 12 was detected in the GIM or CON cells. The data further suggest that both copies of fibroblast chromosome 14 contain an active tumor s uppressor locus and that radiation-induced loss of either fibroblast c hromosome 14 is associated with neoplastic transformation in this syst em, We now conclude that loss of alleles on both fibroblast chromosome 11 and 14 may be required for the radiation-induced neoplastic transf ormation of these human hybrid cells. (C) 1998 by Radiation Research S ociety.