Induction of radioresistance to accelerated carbon-ion beams in recipient cells by nitric oxide excreted from irradiated donor cells of human glioblastoma.
OBJECTIVE
To investigate whether nitric oxide excreted from cells irradiated with accelerated carbon-ion beams modulates cellular radiosensitivity against irradiation in human glioblastoma A-172 and T98G cells.


METHODS
Western-blot analysis of inducible nitric oxide synthase, hsp72 and p53, the concentration assay of nitrite in medium and cell survival assay after irradiation with accelerated carbon-ion beams were performed.


RESULTS
The accumulation of inducible nitric oxide synthase was caused by accelerated carbon-ion beam irradiation of T98G cells but not of A-172 cells. The accumulation of hsp72 and p53 was observed in A-172 cells after exposure to the conditioned medium of the T98G cells irradiated with accelerated carbon-ion beams, and the accumulation was abolished by the addition of an inhibitor for inducible nitric oxide synthase to the medium. The radiosensitivity of A-172 cells was reduced in the conditioned medium of the T98G cells irradiated with accelerated carbon-ion beams compared with conventional fresh growth medium, and the reduction of radiosensitivity was abolished by the addition of an inducible nitric oxide synthase inhibitor to the conditioned medium.


CONCLUSIONS
Nitric oxide excreted from the irradiated donor cells with accelerated carbon-ion beams could modulate the radiosensitivity of recipient cells. These findings indicate the importance of an intercellular signal transduction pathway initiated by nitric oxide in the cellular response to accelerated heavy ions.
Matsumoto
H
H
Department of Experimental Radiology, Fukui Medical University, Matsuoka, Japan. hidekim@fmsrsa.fukui-med.ac.jp
Hayashi
S
S
Hatashita
M
M
Shioura
H
H
Ohtsubo
T
T
Kitai
R
R
Ohnishi
T
T
Yukawa
O
O
Furusawa
Y
Y
Kano
E
E
D015153:Blotting, Western; D002244:Carbon; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D005909:Glioblastoma / Q000532:radiotherapy*; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007477:Ions; D007700:Kinetics; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D020266:Radiotherapy, Conformal; D013997:Time Factors; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014965:X-Rays
D017077:Culture Media, Conditioned; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D007477:Ions; D009573:Nitrites; D016159:Tumor Suppressor Protein p53; D009569:Nitric Oxide; D002244:Carbon; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II