Neoplastic transformation and cytogenetic changes after gamma irradiation of human epithelial cells expressing telomerase.

Neoplastic transformation of human epithelial cells by radiation has previously been investigated using cell lines immortalized with viral vectors. There are disadvantages to this approach, and we report here the results of studies using a human retinal pigment epithelial cell line (340RPE-T53) immortalized by treatment with telomerase. After exposure of the cells to fractionated doses of gamma radiation, there was a marked increase in anchorage-independent growth of the surviving cells. The cloned cell lines derived from these anchorage-independent cultures exhibited an increased growth rate in vitro and were serum-independent compared with the parent cell line. The parent cell line maintained a stable diploid karyotype, The cell lines cloned after irradiation with the lower doses (10 x 2 Gy) were hypodiploid with loss of chromosome 13 and a high level amplification of 10p11.2 associated with a deletion of the remaining short arm segment of chromosome 10 distal to 10p11.2. In contrast, the cell lines cloned after irradiation with the higher doses (15 x 2 Gy) were neartetraploid with derivative chromosomes present characterized by SKY analysis. Thus this human epithelial cell line immortalized with telomerase provides an improved model to investigate mechanisms of radiation carcinogenesis