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

作者：Zvi Fuks, R S Persaud, Alan A. Alfieri, Maureen McLoughlin, Desiree Ehleiter, Jeffrey L. Schwartz, Andrew P. Seddon, Carlos Cordon‐Cardo, Adriana Haimovitz‐Friedman · 发表于：PubMed · 年份：1994 · 被引用次数：331 · 研究领域：Effects of Radiation Exposure、Glutathione Transferases and Polymorphisms、Cancer, Hypoxia, and Metabolism

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 interphas...