Elevation of glutathione in RAW 264.7 cells by low-dose gamma-ray irradiation and its responsibility for the appearance of radioresistance.
We examined the relationship between the induction of glutathione (GSH) level in macrophage-like RAW 264.7 cells by a low (adapting) dose gamma-rays and the cell damage caused by a lethal dose of gamma-rays at various intervals after the adapting dose. The reduced glutathione (GSH) level increased soon after exposure of the cells to 25 cGy of gamma-rays, peaked between 3 hr and 6 hr, and returned almost to the zero time (0 hr) level by 24 hr post-irradiation. Cell damage was assessed by measuring the 3H-thymidine (3H-TdR) incorporation into cellular DNA. gamma-Ray irradiation produced a dose-dependent cell damage in RAW cells, causing about 40% and 60% inhibition of 3H-TdR incorporation into DNA at 1.0 Gy and 2.0 Gy, respectively, as compared with non-irradiated cells. Treatment with the adapting dose of 25 cGy at 1 hr or 24 hr before the lethal irradiation was ineffective. However, pre-irradiation with 25 cGy at 3 hr or 6 hr prior to lethal irradiation inhibited the decrease of 3H-TdR incorporation into DNA, indicating a protective effect. GSH exogenously added to the medium also inhibited the cell damage induced by lethal doses of gamma-Rays in a dose-dependent manner. These results indicate that the induction of endogenous GSH in living cells immediately following low-dose gamma-Ray irradiation is at least partially responsible for the appearance of radioresistance to a subsequent lethal dose of radiation, and may make it possible to use higher doses of radiation in radiotherapy for tumor patients.
Kojima
S
S
Research Institute for Biological Sciences, Science University of Tokyo, Chiba, Japan. kjma@rs.noda.sut.ac.jp
Matsumori
S
S
Ono
H
H
Yamaoka
K
K
D000818:Animals; D002460:Cell Line; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D051379:Mice; D011836:Radiation Tolerance
D005978:Glutathione