Novel concepts in modification of radiation sensitivity.
OBJECTIVE
To determine whether biological effects of radiation, such as apoptosis, that differ from classical clonogenic cell killing, can be modified with agents that would not be expected to modify classical clonogenic cell killing. This would expand the range of potential modifiers of radiation therapy.


METHODS
EL4 murine lymphoma cell apoptosis was determined by electrophoretic analysis of deoxyribonucleic acid (DNA) fragmentation. DNA was extracted 24 h after irradiation or addition of inducing agents. Modifiers of radiation-induced apoptosis were added immediately after irradiation. The effects of radiation on wounded endothelial monolayers were studied by scraping a line across the monolayer 30 min after irradiation. Cell detachment was used as an endpoint to determine the protective effect of prolonged exposure to retinol prior to irradiation.


RESULTS
EL4 cell apoptosis can be induced by tert-butyl hydroperoxide or the glutathione oxidant SR-4077. Radiation-induced EL4 cell apoptosis can be inhibited with 3-aminobenzamide, an agent that sensitizes cells to classical clonogenic cell killing. Radiation-induced endothelial cell detachment from confluent monolayers can be modified by pretreatment with retinol.


CONCLUSIONS
These results raise the possibility that radiation could induce apoptosis by an oxidative stress mechanism that is different from that involved in classical clonogenic cell killing. These and other recent findings encourage the notion that differential modification of classical clonogenic cell killing and other important endpoints of radiation action may be possible.
Bump
E A
EA
Joint Center for Radiation Therapy, Harvard Medical School, Boston, MA 02115.
Braunhut
S J
SJ
Palayoor
S T
ST
Medeiros
D
D
Lai
L L
LL
Cerce
B A
BA
Langley
R E
RE
Coleman
C N
CN
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002417:Cattle; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D003958:Diamide / Q000031:analogs & derivatives / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology; D008223:Lymphoma / Q000473:pathology; D051379:Mice; D010545:Peroxides / Q000494:pharmacology; D011836:Radiation Tolerance / Q000187:drug effects*; D014801:Vitamin A / Q000494:pharmacology; D020122:tert-Butylhydroperoxide
D010545:Peroxides; D003958:Diamide; C050091:diazenedicarboxylic acid bis(N,N-piperidide); D014801:Vitamin A; D004247:DNA; D020122:tert-Butylhydroperoxide