The elimination of low-dose hypersensitivity in Chinese hamster V79-379A cells by pretreatment with X rays or hydrogen peroxide.
To explain increased radioresistance over the X-ray dose range approximately 0.5-1 Gy an inducible radioprotective mechanism triggered by DNA damage was proposed; hypersensitivity to doses << 0.5 Gy reflected the response prior to the activation of this system (Marples and Joiner, Radiat. Res. 133, 41-51, 1993). To test this hypothesis, cells were pre-exposed to DNA-damaging agents in an attempt to induce the process prematurely. An increase in survival was evident at X-ray doses below 0.3 Gy after a priming treatment of X rays (0.05, 0.2, 1 Gy) given 6 h earlier. The protective effect was found to be transitory, requiring time for development and diminishing after two to three cell cycle times. Cycloheximide administered in the interval between the priming and challenge doses of X rays abolished the protection conferred by pretreatment, indicating the involvement of de novo protein synthesis. Oxidative damage by nontoxic doses of hydrogen peroxide (10(-4) M, but not 10(-6) M) also produced a protective effect against subsequent X irradiation. These experiments indicate survival in the hyper-radiosensitive region (<< 0.5 Gy) can be modified by pretreatment with agents known to affect DNA repair. In addition, the development of increased radioresistance after single doses of X rays was inhibited by cycloheximide treatment. These studies provide evidence to support the explanations proposed previously for the phenomena of increased radioresistance and hyper-radiosensitivity observed at very low X-ray doses.
Marples
B
B
Department of Medical Biophysics, British Columbia Cancer Research Centre, Vancouver, Canada.
Joiner
M C
MC
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D003513:Cycloheximide / Q000494:pharmacology; D004249:DNA Damage; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D011829:Radiation Dosage; D011836:Radiation Tolerance; D014965:X-Rays
D003513:Cycloheximide; D006861:Hydrogen Peroxide