Basic fibroblast growth factor protects endothelial cells against radiation-induced programmed cell death in vitro and in vivo

Zvi Fuks, Roger S. Persaud, Alan Alfieri, Maureen McLoughlin, Desiree Ehleiter, Jeffery L. Schwartz, Andrew P. Seddon, Carlos Cordon-Cardo, Adriana Haimovitz-Friedman

Research output: Contribution to journalArticle

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Abstract

Apoptosis (programmed cell death) serves as a common mechanism of interphase cell death after radiation exposure in thymic, lymphoid, and hematopoietic cells but has infrequently been documented in other adult mammalian cell types. The present study demonstrates that apoptotic interphase cell death occurs in endothelial cells after exposure to clinically relevant radiation doses and that basic fibroblast growth factor (bFGF) protects endothelial cells against this mode of the lethal effects of radiation. Radiation exposure produced heterologous double-stranded DNA breaks in endothelial cells, but the cells exhibited a similar competence for repair of this damage in the presence or absence of bFGF. However, subsequent to the completion of this repair process, a second process of DNA fragmentation became apparent, which was detected only in the absence of bFGF and was associated with a DNA ladder of oligonucleosomal fragments characteristic of apoptosis. The apoptotic DNA degradation occurred mainly in G0-G1 phase cells and was inhibited by bFGF stimulation. C3H/HeJ mice exposed to lethal doses of whole lung irradiation exhibited similar apoptotic changes in the endothelial cell lining of the pulmonary microvasculature within 6-8 h after radiation exposure. bFGF given i.v. immediately before and after irradiation inhibited the development of apoptosis in these cells and protected mice against the development of lethal radiation pneumonitis. These findings suggest that interphase apoptosis may represent a biologically relevant mechanism of radiation-induced cell kill in nonlymphoid mammalian cells both in vitro and in vivo and that natural protection mechanisms against this effect may be associated with the level of radiation resistance in normal and malignant tissues in vivo.

Original languageEnglish (US)
Pages (from-to)2582-2590
Number of pages9
JournalCancer Research
Volume54
Issue number10
StatePublished - May 15 1994
Externally publishedYes

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Fibroblast Growth Factor 2
Cell Death
Endothelial Cells
Radiation
Interphase
Apoptosis
DNA Fragmentation
Radiation Pneumonitis
Lung
Cell Cycle Resting Phase
Double-Stranded DNA Breaks
Inbred C3H Mouse
Radiation Effects
G1 Phase
Microvessels
Mental Competency
In Vitro Techniques
Lymphocytes
DNA
Radiation Exposure

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Fuks, Z., Persaud, R. S., Alfieri, A., McLoughlin, M., Ehleiter, D., Schwartz, J. L., ... Haimovitz-Friedman, A. (1994). Basic fibroblast growth factor protects endothelial cells against radiation-induced programmed cell death in vitro and in vivo. Cancer Research, 54(10), 2582-2590.

Basic fibroblast growth factor protects endothelial cells against radiation-induced programmed cell death in vitro and in vivo. / Fuks, Zvi; Persaud, Roger S.; Alfieri, Alan; McLoughlin, Maureen; Ehleiter, Desiree; Schwartz, Jeffery L.; Seddon, Andrew P.; Cordon-Cardo, Carlos; Haimovitz-Friedman, Adriana.

In: Cancer Research, Vol. 54, No. 10, 15.05.1994, p. 2582-2590.

Research output: Contribution to journalArticle

Fuks, Z, Persaud, RS, Alfieri, A, McLoughlin, M, Ehleiter, D, Schwartz, JL, Seddon, AP, Cordon-Cardo, C & Haimovitz-Friedman, A 1994, 'Basic fibroblast growth factor protects endothelial cells against radiation-induced programmed cell death in vitro and in vivo', Cancer Research, vol. 54, no. 10, pp. 2582-2590.
Fuks Z, Persaud RS, Alfieri A, McLoughlin M, Ehleiter D, Schwartz JL et al. Basic fibroblast growth factor protects endothelial cells against radiation-induced programmed cell death in vitro and in vivo. Cancer Research. 1994 May 15;54(10):2582-2590.
Fuks, Zvi ; Persaud, Roger S. ; Alfieri, Alan ; McLoughlin, Maureen ; Ehleiter, Desiree ; Schwartz, Jeffery L. ; Seddon, Andrew P. ; Cordon-Cardo, Carlos ; Haimovitz-Friedman, Adriana. / Basic fibroblast growth factor protects endothelial cells against radiation-induced programmed cell death in vitro and in vivo. In: Cancer Research. 1994 ; Vol. 54, No. 10. pp. 2582-2590.
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