Basic fibroblast growth factor protects endothelial cells against radiation-induced programmed cell death in vitro and in vivo Journal Article
| Authors: | Fuks, Z.; Persaud, R. S.; Alfieri, A.; McLoughlin, M.; Ehleiter, D.; Schwartz, J. L.; Seddon, A. P.; Cordon-Cardo, C.; Haimovitz-Friedman, A. |
| Article Title: | Basic fibroblast growth factor protects endothelial cells against radiation-induced programmed cell death in vitro and in vivo |
| 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 oligonudeosomal fragments characteristic of apoptosis. The apoptotic DNA degradation occurred mainly in Go-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 cefl lining of the pulmonary microvasculature within 6-8 h after radiation exposure. bFGF given Lv. immediately before and after irradiation inhibited the development of apoptosis in these eels and protected mice against the development of lethal radiation pneumonitis. These findings suggest that interphase apoptosis may represent a biologicaly relevant mechanism of radiation-induced cefl 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. © 1994, American Association for Cancer Research. All rights reserved. |
| Keywords: | controlled study; dose response; nonhuman; radiation dose; flow cytometry; animal cell; mouse; animals; mice; animal tissue; dna damage; cell survival; dna repair; apoptosis; animal model; radiation exposure; time factors; dose-response relationship, radiation; dna strand breakage; pneumonia; endothelium cell; fibroblast growth factor 2; dna; double stranded dna; drug distribution; endothelium, vascular; diagnosis; lung; fluorescence microscopy; cattle; drug therapy; dna nick translation; intravenous drug administration; injections, intravenous; lung blood vessel; dna fragment; mice, inbred c3h; prevention; etiology; agar gel electrophoresis; interphase; radiation pneumonitis; basic fibroblast growth factor; dna content; male; priority journal; article |
| Journal Title: | Cancer Research |
| Volume: | 54 |
| Issue: | 10 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 1994-05-15 |
| Start Page: | 2582 |
| End Page: | 2590 |
| Language: | English |
| PROVIDER: | scopus |
| PUBMED: | 8168084 |
| DOI/URL: | |
| Notes: | Export Date: 14 January 2019 -- Article -- Source: Scopus |
Citation Impact
MSK Authors
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428Fuks -
612Cordon-Cardo -
25
Ehleiter -
17
McLoughlin -
7
Persaud -
35Alfieri
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