Radiobiology of normal tissues and
radiation protection

Prof. Wolfgang Dörr Group Leader Phone: 0351 458 3390 mailto: doerr@rcs.urz.tu-dresden.de

Normal tissue effects in vivo (animal models, patients) of radiation exposure - pathogenesis, regulatory processes, influencing factors - and potential strategies for their modification are one research focus of this group. A second line of research concentrates on radiation protection issues. Specific research topics are:
Characterisation of signalling cascades involved in the radiation pathogenesis of specific tissues in vivo (oral mucosa, gut, skin, lung, urinary bladder, heart)
Modulation of normal tissue effects by specific, biology-driven intervention in these signalling cascades Identification of factors involved in the development of second cancers in radiotherapy patients and estimation of risk parameters.

Studies on functional, clinically relevant endpoints, such as confluent oral mucositis, skin ulceration, urinary bladder compliance/micturition frequency, or heart function, are accompanied by histological and immunohistochemical investigations. Participation in clinical studies illustrates the translational aspect of the research. In cooperation with the Department of Radiation Oncology, Medical University Vienna, parameters for the manifestation of normal tissue effects are analyzed. The intensive mouth care programme for patients with head-and-neck malignancies of the Department of Radiotherapy and Radiation Oncology, Medical Faculty Carl Gustav Carus Dresden, complements the preclinical studies on oral mucositis and assists in validating the preclinical results. Some examples of research projects are illustrated below.

One approach to ameliorate radiation effects in (proliferating) normal tissues is the modulation of growth factor signalling, either by administration of growth factors or by inhibition of their receptors. In oral mucosa and urinary bladder, the protective potential of Keratinocyte Growth Factor (Palifermin) has been demonstrated in combination with single radiation exposure as well as with fractionated irradiation (fig. 1).

The role of haematopoietic or mesenchymal stem cells for normal tissue reactions was exemplified in oral mucosa, as part of a European cooperation (EU FP6: FIRST). For this, stem cells were either transplanted or mobilised from the bone marrow. With both approaches, a significant reduction of oral mucositis was observed. One example is illustrated in figure 2.

Figure 1: Effect of Palifermin administration in combination with daily fractionated irradiation (10x3 Gy, days 0-4/7-11)
Tongue mucosa (mouse) were irradiated daily over 2 weeks, followed by test irradiation with graded doses. Palifermin was administered on 3 or 4 consecutive weekends, subcutaneously at the days indicated at the abscissa. Error bars represent the standard deviation σ of the ED50-values, as computed by probit analyses. The shaded area reflects the ED50±σ for test irradiation after 10x3.0 Gy in 2 weeks without application of palifermin.

Figure 2: Effect of bone marrow transplantation at various days of fractionated irradiation (15x3 Gy/3 weeks)
Oral mucosa (mouse) was irradiated daily over 3 weeks, followed by graded test doses. Transplantation of bone marrow from genetically identical donor mice was performed at the days indicated at the abscissa. Error bars represent the standard deviation σ of the ED50-values, as computed by probit analyses. The shaded area reflects the ED50±σ for test irradiation after 10x3.0 Gy in 2 weeks without bone marrow transplantation.