Constitutive nitric oxide acting as a possible intercellular signaling molecule in the initiation of radiation-induced DNA double strand breaks in non-irradiated bystander cells.
The initiation and propagation of the early processes of bystander signaling induced by low-dose alpha-particle irradiation are very important for understanding the underlying mechanism of the bystander process. Our previous investigation showed that the medium collected from cell culture exposed to low-dose alpha-particle rapidly induced phosphorylated form of H2AX protein foci formation among the non-irradiated medium receptor cells in a time-dependent manner. Using N(G)-methyl-L-arginine, 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate and N(omega)-nitro-L-arginine (L-NNA) treatment before exposure to 1 cGy alpha-particle, we showed in the present study that nitric oxide (NO(*)) produced in the irradiated cells was important and necessary for the DNA double strand break inducing activity (DIA) of conditioned medium and the generation of NO(*) in irradiated confluent AG1522 cells is in a time-dependent manner and that almost all NO(*) was generated within 15 min post-irradiation. Concurrently, the kinetics of NO(*) production in the medium of irradiated cells after irradiation was rapid and in a time-dependent manner as well, with a maximum yield observed at 10 min after irradiation with electron spin resonance analysis. Furthermore, our results that 7-Nitroindazole and L-NNA, but not aminoguanidine hemisulfate, treatment before exposure to 1 cGy alpha-particle significantly decrease the DIA of the conditioned medium suggested that constitutive NO(*) from the irradiated cells possibly acted as an intercellular signaling molecule to initiate and activate the early process (<or=30 min) of bystander response after low-dose irradiation.
Han
W
W
Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei, People's Republic of China.
Wu
L
L
Chen
S
S
Bao
L
L
Zhang
L
L
Jiang
E
E
Zhao
Y
Y
Xu
A
A
Hei
T K
TK
Yu
Z
Z
D000512:Alpha Particles; D024201:Bystander Effect / Q000235:genetics*; D002460:Cell Line; D004249:DNA Damage; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D006657:Histones / Q000528:radiation effects; D006801:Humans; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D015398:Signal Transduction; D012867:Skin / Q000166:cytology / Q000528:radiation effects
C468783:H2AX protein, human; D006657:Histones; D020030:Nitric Oxide Donors; D009569:Nitric Oxide