Loss of suppressor loci on chromosomes 11 and 14 may be required for radiation-induced neoplastic transformation of HeLa x skin fibroblast human cell hybrids

Marc Mendonca, Kelly Howard, Clare L. Fasching, Daphne L. Farrington, Lael A. Desmond, Eric J. Stanbridge, J. Leslie Redpath

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

We have previously reported a linkage between radiation-induced damage to a putative tumor suppressor locus on fibroblast chromosome 11 and the re- expression of tumorigenicity in a hybrid cell line (HeLa x human skin fibroblast) used to study neoplastic transformation. Further investigation into the molecular basis of radiation-induced neoplastic transformation of the hybrid cell, CGL1, indicates that loss of fibroblast chromosome 11 appears to be necessary but not sufficient for neoplastic transformation. Previous analysis had suggested, though not clearly demonstrated, a possible role for loss of alleles on fibroblast chromosome 14 in the neoplastic transformation of the hybrid cells. Therefore, the status of chromosome 14 in the γ-ray-induced, neoplastically transformed (GIM) hybrid cell lines and in nontumorigenic control (CON) hybrid cell lines isolated from irradiated populations has been investigated. Chromosome painting and molecular studies using restriction fragment length polymorphisms and tetranucleotide repeat polymorphism 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 chromosome 12 was detected in the GIM or CON cells. The data further suggest that both copies of fibroblast chromosome 14 contain an active tumor suppressor locus and that radiation-induced loss of either fibroblast chromosome 14 is associated with neoplastic transformation in this system. We now conclude that loss of alleles on both fibroblast chromosome 11 and 14 may be required for the radiation-induced neoplastic transformation of these human hybrid cells.

Original languageEnglish
Pages (from-to)246-255
Number of pages10
JournalRadiation Research
Volume149
Issue number3
DOIs
StatePublished - 1998

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suppressors
Chromosomes, Human, Pair 14
Chromosomes, Human, Pair 11
Hybrid Cells
chromosomes
fibroblasts
loci
skin (animal)
Fibroblasts
Radiation
Skin
radiation
cultured cells
cell lines
Cell Line
cells
Chromosomes, Human, Pair 12
polymorphism
Alleles
Chromosome Painting

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Radiology Nuclear Medicine and imaging
  • Biophysics
  • Radiation

Cite this

Loss of suppressor loci on chromosomes 11 and 14 may be required for radiation-induced neoplastic transformation of HeLa x skin fibroblast human cell hybrids. / Mendonca, Marc; Howard, Kelly; Fasching, Clare L.; Farrington, Daphne L.; Desmond, Lael A.; Stanbridge, Eric J.; Leslie Redpath, J.

In: Radiation Research, Vol. 149, No. 3, 1998, p. 246-255.

Research output: Contribution to journalArticle

Mendonca, Marc ; Howard, Kelly ; Fasching, Clare L. ; Farrington, Daphne L. ; Desmond, Lael A. ; Stanbridge, Eric J. ; Leslie Redpath, J. / Loss of suppressor loci on chromosomes 11 and 14 may be required for radiation-induced neoplastic transformation of HeLa x skin fibroblast human cell hybrids. In: Radiation Research. 1998 ; Vol. 149, No. 3. pp. 246-255.
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