Analysis of the mechanism underlying radiation-induced jaw bone necrosis

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The mechanism underlying radiation-induced bone necrosis was studied using mouse marrow- derived osteoblast-like cells. Prophylactic drug therapy for such necrosis was also studied.The percentage of osteoblast-like cells that remained viable after radiation exposure was found to correlate with a decrease in the amount of DNA, and the decrease in amount of DNA was correlated with the radiation dose. The DNA cleavage rate, as measured by the fluorescence method, increased as the radiation dose increased. When DNA fragmentation was examined by enzyme immunoassay using BrdU labeling, the amount of DNA fragments in the culture supernatants increased with time, suggesting that the fragments represented cell membrane destruction associated with the loss of cell viability. Analysis of the DNA cleavage patterns using agarose gel electrophoresis revealed nonspecific cleavage of the singlet chain at all radiation dose levels examined. These results suggest that the loss of viability of osteoblasts due to non-specific DNA cleavage induced by radiation underlies radiation-induced bone necrosis. When used independently, ipriflavone markedly elevated the cell viability rate of osteoblast-like cells. Vitamin D_3 exerted a similar effect when used in combination with a herbal preparation named Hachimijiogan. When the effects of these drugs on DNA fragmentation were examined, it was found that the cell membrane remained intact in all of the Hachimijiogan-treated cells which lost their viability following irradiation. Following treatment with ipriflavone, cell necrosis induced by 5 Gy radiation was not associated with cell membrane damage. On the other hand, following treatment with vitamin D_3, cell necrosis induced by radiation was associated with cell membrane damage at all the radiation dose levels examined. These results suggest that treatment with ipriflavone or a combination of vitamin D_3 and Hachimijiogan may be useful for the prevention of radiation-induced bone necrosis.