Evidence for a role of delayed death and genomic instability in radiation-induced neoplastic transformation of human hybrid cells

Marc Mendonca, T. M. Temples, D. L. Farrington, C. Bloch

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

HeLa x skin fibroblast human hybrid cells have been developed into a model of radiation-induced neoplastic transformation. The authors' studies indicate that the loss of putative tumour suppressor loci on fibroblast chromosomes 11 and 14 is evident after radiation-induced neoplastic transformation. How these fibroblast chromosomes/putative tumour suppressor loci are lost after radiation exposure is currently being investigated. It has been shown that the appearance of transformed foci correlates with the onset of the delayed reduction in plating efficiency or delayed death. This delayed death appears to be the result of the onset of a novel delayed apoptosis in the irradiated progeny beginning around day 8 post-irradiation. It was proposed that the reduction in plating efficiency and subsequent neoplastic transformation are all the result of a radiation-induced genomic instability. The instability process has two relevant outcomes: (1) cell death due to the induction of a delayed apoptosis in cells; and (2) neoplastic transformation of a small subset of survivors that have lost fibroblast chromosomes 11 and 14 (tumour suppressor loci) but either have not acquired enough genetic damage to induce the apoptotic response or have undergone molecular changes allowing them to bypass apoptosis. Data from the genomic instability and delayed death literature will be reviewed in terms of relevance to radiation-induced neoplastic transformation. New data are presented which demonstrate that use of growth media supplemented with a specific lot of calf serum was found to increase the number of cells undergoing radiation-induced neoplastic transformation, compared with standard serum after a fixed dose of radiation. This correlates with an increase in delayed death in the irradiated progeny which the authors propose is the result of increased genomic instability postirradiation of cells grown in this serum. Preliminary data are presented indicating that a delayed apoptosis is also seen after high-energy He- particle exposure in this system.

Original languageEnglish
Pages (from-to)755-764
Number of pages10
JournalInternational Journal of Radiation Biology
Volume74
Issue number6
StatePublished - 1998

Fingerprint

Hybrid Cells
Genomic Instability
death
fibroblasts
apoptosis
Cell death
Cells
Radiation
genomics
suppressors
Fibroblasts
chromosomes
radiation
loci
cells
serums
Apoptosis
neoplasms
Chromosomes
Chromosomes, Human, Pair 14

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology
  • Nuclear Energy and Engineering
  • Radiation

Cite this

Evidence for a role of delayed death and genomic instability in radiation-induced neoplastic transformation of human hybrid cells. / Mendonca, Marc; Temples, T. M.; Farrington, D. L.; Bloch, C.

In: International Journal of Radiation Biology, Vol. 74, No. 6, 1998, p. 755-764.

Research output: Contribution to journalArticle

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