Re-assessment of chronic radio-induced tissue damage in a rat hindlimb model.

Radiotherapy is successfully used to treat neoplastic lesions, but may adversely affect normal tissues within the irradiated volume. However, additional clinical and para-clinical data are required for a comprehensive understanding of the pathogenesis of this damage. We assessed a rat model using clinical records and medical imaging to gain a better understanding of irradiation-induced tissue damage. The hindlimbs of the rats in this model were irradiated with a single dose of 30 or 50 Gy. Sequential analysis was based on observation records of stage and planar scintigraphy. Additional radiography, radiohistology and histology studies were performed to detect histological alterations. All animals developed acute and late effects, with an increased severity after a dose of 50 Gy. The bone uptake of (99m)Tc-HDP was significantly decreased in a dose- and time-dependent manner. Histologically, significant tissue damage was observed. After the 50 Gy irradiation, the animals developed lesions characteristic of osteoradionecrosis (ORN). Radiographic and histological studies provided evidence of lytic bone lesions. Our rat model developed tissue damage characteristic of radiation injury after a single 30 Gy irradiation and tissue degeneration similar to that which occurs during human ORN after a 50 Gy irradiation. The development of this animal model is an essential step in exploring the pathogenesis of irradiation-induced tissue damage, and may be used to test the efficacy of new treatments.

[1]  N. Ghazali,et al.  Osteoradionecrosis of the jaws: current understanding of its pathophysiology and treatment. , 2008, The British journal of oral & maxillofacial surgery.

[2]  R. Sader,et al.  Management of osteoradionecrosis of the jaws: an analysis of evidence. , 2008, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[3]  Bernhard Kimmig,et al.  HDR brachytherapy irradiation of the jaw - as a new experimental model of radiogenic bone damage. , 2008, Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery.

[4]  S. François,et al.  Human mesenchymal stem cells favour healing of the cutaneous radiation syndrome in a xenogenic transplant model , 2006, Annals of Hematology.

[5]  Nguyen Tran,et al.  Feasibility of in vivo dual-energy myocardial SPECT for monitoring the distribution of transplanted cells in relation to the infarction site , 2006, European Journal of Nuclear Medicine and Molecular Imaging.

[6]  N. Demirkan,et al.  The preventive effect of vitamin D3 on radiation-induced hair toxicity in a rat model. , 2006, Life sciences.

[7]  N. Futran,et al.  Osteoradionecrosis of the mandible , 2005, Current opinion in otolaryngology & head and neck surgery.

[8]  C Norman Coleman,et al.  Effects of radiation on normal tissue: consequences and mechanisms. , 2003, The Lancet. Oncology.

[9]  U. Mende,et al.  Osteoradionecrosis of the jaws as a side effect of radiotherapy of head and neck tumour patients--a report of a thirty year retrospective review. , 2003, International journal of oral and maxillofacial surgery.

[10]  R. Orecchia,et al.  Radiotherapy-induced mandibular bone complications. , 2002, Cancer treatment reviews.

[11]  E. Travis Organizational response of normal tissues to irradiation. , 2001, Seminars in radiation oncology.

[12]  M. Boysen,et al.  Mandibular osteoradionecrosis: clinical behaviour and diagnostic aspects. , 2000, Clinical otolaryngology and allied sciences.

[13]  C. Muro-Cacho,et al.  Radiation effects on osteoblasts in vitro: a potential role in osteoradionecrosis. , 2000, Archives of otolaryngology--head & neck surgery.

[14]  M. S. Lee,et al.  Radiation-induced muscle damage in rats after fractionated high-dose irradiation. , 1998, Radiation research.

[15]  R. Rössler,et al.  The role of magnetic resonance imaging and scintigraphy in the diagnosis of pathologic changes of the mandible after radiation therapy. , 1996, International journal of oral and maxillofacial surgery.

[16]  T. Yamamuro,et al.  Long-term changes in the haversian systems following high-dose irradiation. An ultrastructural and quantitative histomorphological study. , 1994, The Journal of bone and joint surgery. American volume.

[17]  Y. Shibamoto,et al.  Osteocyte viability after high-dose irradiation in the rabbit. , 1993, Clinical orthopaedics and related research.

[18]  Y. Shibamoto,et al.  Changes in bone after high-dose irradiation. Biomechanics and histomorphology. , 1991, The Journal of bone and joint surgery. British volume.

[19]  J. V. van Merkesteyn,et al.  Osteoradionecrosis of the mandible: pathogenesis. , 1990, American journal of otolaryngology.

[20]  P. Jarritt,et al.  The investigation of osteoradionecrosis of the mandible by 99mTc-methylene diphosphonate radionuclide bone scans. , 1990, The British journal of oral & maxillofacial surgery.

[21]  E. Chao,et al.  Effects of irradiation on cortical bone and their time-related changes. A biomechanical and histomorphological study. , 1988, The Journal of bone and joint surgery. American volume.

[22]  R. Marx,et al.  Studies in the radiobiology of osteoradionecrosis and their clinical significance , 1987 .

[23]  R. Marx A new concept in the treatment of osteoradionecrosis. , 1983, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[24]  M. King,et al.  A study of irradiated bone: I. histopathologic and physiologic changes. , 1979, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[25]  J. Brady,et al.  Long-term effects of radiation on the vascularity of rat bone--quantitative measurements with a new technique. , 1971, Radiation research.

[26]  R. Baserga,et al.  The delayed effects of external gamma irradiation on the bones of rats. , 1961, The American journal of pathology.

[27]  A. Mueller,et al.  Head and neck cancer in Germany: a site-specific analysis of survival of the Thuringian cancer registration database , 2009, Journal of Cancer Research and Clinical Oncology.

[28]  W. Small,et al.  Radiation-induced skeletal injury. , 2006, Cancer treatment and research.

[29]  G. Granström,et al.  Osteoradionecrosis of the mandible: a microradiographic study of cortical bone. , 1999, Scandinavian journal of plastic and reconstructive surgery and hand surgery.

[30]  I. Turesson,et al.  Bone cell viability after irradiation. An enzyme histochemical study. , 1987, Acta oncologica.

[31]  B. Powers,et al.  A REVIEW OF THE EFFECTS OF RADIATION THERAPY ON BONE , 1987 .

[32]  J. Hopewell,et al.  Functional changes in the vascularity of the irradiated rat femur. Implications for late effects. , 1983, Acta radiologica. Oncology.

[33]  M. King,et al.  A study of irradiated bone. Part II. changes in Tc-99m pyrophosphate bone imaging. , 1980, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[34]  E. Cronkite,et al.  Radiation-induced damage to blood vessels: a study of dose--effect relationship with time after X-irradiation. , 1978, International journal of radiation biology and related studies in physics, chemistry, and medicine.

[35]  G. Grimm [Animal experimental studies on the pathogenesis of radiogenic bone injuries in the mandibles of adult rabbits. II. Histometric data]. , 1970, Deutsche Zahn-, Mund-, und Kieferheilkunde mit Zentralblatt fur die gesamte Zahn-, Mund-, und Kieferheilkunde.