Human fibroblasts transfected with an ATM antisense vector respond abnormally to ionizing radiation.

  • Authors:
    • N Uhrhammer
    • E Fritz
    • L Boyden
    • M S Meyn
  • View Affiliations

  • Published online on: July 1, 1999     https://doi.org/10.3892/ijmm.4.1.43
  • Pages: 43-50
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Abstract

ATM, the gene mutated in ataxia-telangiectasia (A-T), mediates multiple cellular responses to DNA damage. A-T homozygotes have a high risk of cancer and exhibit spontaneous chromosomal instability, and cultured A-T cells react abnormally to ionizing radiation. We have developed an ATM antisense vector that confers an A-T phenotype on normal cells. An episomal antisense vector was created that contained a 1.3 kb segment of the ATM cDNA, and was transfected into normal human fibroblasts. Intracellular levels of ATM protein were typically reduced 10-fold in antisense-expressing (GM639-46alpha) clones. GM639-46alpha clones exhibited the low threshold for radiation-induced apoptosis, low clonogenic survival, and cell cycle defects normally seen in A-T cells. Transfection with the corresponding ATM sense strand vector had no effect on the behavior of normal cells, and neither vector affected the behavior of A-T cells. Our results demonstrate that interference with ATM gene expression recreates the A-T phenotype in normal cells, and provide functional evidence linking the ATM gene to cellular DNA damage responses. The ATM antisense vector should prove a useful tool for studying ATM function in a variety of normal, mutant, and malignant cell lines.

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Jul 1999
Volume 4 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Uhrhammer N, Fritz E, Boyden L and Meyn M: Human fibroblasts transfected with an ATM antisense vector respond abnormally to ionizing radiation.. Int J Mol Med 4: 43-50, 1999.
APA
Uhrhammer, N., Fritz, E., Boyden, L., & Meyn, M. (1999). Human fibroblasts transfected with an ATM antisense vector respond abnormally to ionizing radiation.. International Journal of Molecular Medicine, 4, 43-50. https://doi.org/10.3892/ijmm.4.1.43
MLA
Uhrhammer, N., Fritz, E., Boyden, L., Meyn, M."Human fibroblasts transfected with an ATM antisense vector respond abnormally to ionizing radiation.". International Journal of Molecular Medicine 4.1 (1999): 43-50.
Chicago
Uhrhammer, N., Fritz, E., Boyden, L., Meyn, M."Human fibroblasts transfected with an ATM antisense vector respond abnormally to ionizing radiation.". International Journal of Molecular Medicine 4, no. 1 (1999): 43-50. https://doi.org/10.3892/ijmm.4.1.43