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Effects of irradiation on growing bones.

Hans Engström

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Abstract

The effects of irradiation on various tissues have been studied extensively. Nonetheless, the metabolism in growing bones has not been evaluated in a systematic way after moderate doses of irradiation. It was found that scattered radiation, that reaches the oral region during radiotherapy of malignancies outside the oral region, causes absorbed doses within the range of 0.2-20 Gy, while absorbed doses from radiography in orthodontics were only 30-40 mGy. Bone formation in the metaphyseal area of rat tibia in vivo after irradiation with 0.5-8 Gy was determined by a tetracycline labelling method. Five and 8 Gy induced a significant growth retardation. This was detectable already after 36 hours and was maximal 7-14 days after irradiation. Between 14 and 30 days following irradiation growth was normalized. Alkaline phosphatase (ALP) activity in bone was evaluated biochemically and decreased one day after irradiation with 0.5-8 Gy. This was followed by a gradual increase in ALP activity and a return to normal values 30 days after irradiation. Histochemical studies of the rat tibias included evaluation of ALP, acid phosphatase, NADH2-diaphorase and Glucose-6 phosphate dehydrogenase. A decrease in ALP activity one day after irradiation was observed with 5, 8, and 10 Gy. Acid phosphatase and the two oxidative enzymes were increased in activity during the entire 7-day experimental period, reflecting an altered metabolism. Normal activities of all the studied enzymes were observed 30 days after irradiation. Results from suture area and synchondrosis area as evaluated by histochemistry and a cephalometric radiographic method showed that early transient metabolic changes occurred in the craniofacial growth sites after irradiation with 5 and 8 Gy. The morphological changes observed in anatomical regions within the irradiated field (neurocranium) persisted in contrast to the changes in the viscerocranium that were normalized at the end of the experimental period. An in vitro system was used to examine the effects of irradiation on certain aspects of bone growth. Mice calvaria were irradiated in vitro with 2 or 10 Gy. A different response in suture and bone was found 3 hours to 4 days after irradiation. Bone was affected by 2 Gy, but not the suture. Thus, the suture seems to be an area with more radioresistant fibroblast-like cells than the cortical bone, which indicates a difference in radiosensitivity of the cells in these two growth sites. The conclusions from the present thesis are that irradiation with 2-10 Gy of bone both in organ culture and in experimental animals induces metabolic and morphologic changes which were detected early and were transient.

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The effects of irradiation on various tissues have been studied extensively. Nonetheless, the metabolism in growing bones has not been evaluated in a systematic way after moderate doses of irradiation. It was found that scattered radiation, that reaches the oral region during radiotherapy of malignancies outside the oral region, causes absorbed doses within the range of 0.2-20 Gy, while absorbed doses from radiography in orthodontics were only 30-40 mGy. Bone formation in the metaphyseal area of rat tibia in vivo after irradiation with 0.5-8 Gy was determined by a tetracycline labelling method. Five and 8 Gy induced a significant growth retardation. This was detectable already after 36 hours and was maximal 7-14 days after irradiation. Between 14 and 30 days following irradiation growth was normalized. Alkaline phosphatase (ALP) activity in bone was evaluated biochemically and decreased one day after irradiation with 0.5-8 Gy. This was followed by a gradual increase in ALP activity and a return to normal values 30 days after irradiation. Histochemical studies of the rat tibias included evaluation of ALP, acid phosphatase, NADH2-diaphorase and Glucose-6 phosphate dehydrogenase. A decrease in ALP activity one day after irradiation was observed with 5, 8, and 10 Gy. Acid phosphatase and the two oxidative enzymes were increased in activity during the entire 7-day experimental period, reflecting an altered metabolism. Normal activities of all the studied enzymes were observed 30 days after irradiation. Results from suture area and synchondrosis area as evaluated by histochemistry and a cephalometric radiographic method showed that early transient metabolic changes occurred in the craniofacial growth sites after irradiation with 5 and 8 Gy. The morphological changes observed in anatomical regions within the irradiated field (neurocranium) persisted in contrast to the changes in the viscerocranium that were normalized at the end of the experimental period. An in vitro system was used to examine the effects of irradiation on certain aspects of bone growth. Mice calvaria were irradiated in vitro with 2 or 10 Gy. A different response in suture and bone was found 3 hours to 4 days after irradiation. Bone was affected by 2 Gy, but not the suture. Thus, the suture seems to be an area with more radioresistant fibroblast-like cells than the cortical bone, which indicates a difference in radiosensitivity of the cells in these two growth sites. The conclusions from the present thesis are that irradiation with 2-10 Gy of bone both in organ culture and in experimental animals induces metabolic and morphologic changes which were detected early and were transient.

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Available abstract

The effects of irradiation on various tissues have been studied extensively. Nonetheless, the metabolism in growing bones has not been evaluated in a systematic way after moderate doses of irradiation. It was found that scattered radiation, that reaches the oral region during radiotherapy of malignancies outside the oral region, causes absorbed doses within the range of 0.2-20 Gy, while absorbed doses from radiography in orthodontics were only 30-40 mGy. Bone formation in the metaphyseal area of rat tibia in vivo after irradiation with 0.5-8 Gy was determined by a tetracycline labelling method. Five and 8 Gy induced a significant growth retardation. This was detectable already after 36 hours and was maximal 7-14 days after irradiation. Between 14 and 30 days following irradiation growth was normalized. Alkaline phosphatase (ALP) activity in bone was evaluated biochemically and decreased one day after irradiation with 0.5-8 Gy. This was followed by a gradual increase in ALP activity and a return to normal values 30 days after irradiation. Histochemical studies of the rat tibias included evaluation of ALP, acid phosphatase, NADH2-diaphorase and Glucose-6 phosphate dehydrogenase. A decrease in ALP activity one day after irradiation was observed with 5, 8, and 10 Gy. Acid phosphatase and the two oxidative enzymes were increased in activity during the entire 7-day experimental period, reflecting an altered metabolism. Normal activities of all the studied enzymes were observed 30 days after irradiation. Results from suture area and synchondrosis area as evaluated by histochemistry and a cephalometric radiographic method showed that early transient metabolic changes occurred in the craniofacial growth sites after irradiation with 5 and 8 Gy. The morphological changes observed in anatomical regions within the irradiated field (neurocranium) persisted in contrast to the changes in the viscerocranium that were normalized at the end of the experimental period. An in vitro system was used to examine the effects of irradiation on certain aspects of bone growth. Mice calvaria were irradiated in vitro with 2 or 10 Gy. A different response in suture and bone was found 3 hours to 4 days after irradiation. Bone was affected by 2 Gy, but not the suture. Thus, the suture seems to be an area with more radioresistant fibroblast-like cells than the cortical bone, which indicates a difference in radiosensitivity of the cells in these two growth sites. The conclusions from the present thesis are that irradiation with 2-10 Gy of bone both in organ culture and in experimental animals induces metabolic and morphologic changes which were detected early and were transient.

Key concepts: Alkaline phosphatase, Irradiation, Acid phosphatase, Chemistry, Tibia, In vivo, Enzyme, Biochemistry

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