ARCON in experimental and clinical radiotherapy

.............................................................................................................................................................................. 3 List of papers .................................................................................................................................................................. 4 Abbreviations ................................................................................................................................................................. 5 Introduction ..................................................................................................................................................................... 6 Historical perspective ..................................................................................................................................... 6 Normobaric oxygen and carbogen as radiosensitizers .................................................... 7 Nicotinamide as radiosensitizer ............................................................................................................ 7 Carbogen and nicotinamide (CON) as radiosensitizers .................................................... 8 ARCON in experimental and pre-clinical radiotherapy ..................................................... 8 Current research .................................................................................................................................................. 9 Paper I. Carbogen and nicotinamide as radiosensitizers in conventional and accelerated radiotherapy ..................................................................10 Paper II. Is sensitization with nicotinamide and carbogen dependent on nicotinamide concentration at the time of irradiation? ..................................... 10 Paper III. Radiosensitisation in normal tissues with oxygen, carbogen and nicotinamide: therapeutic gain comparisons for fractionated X-ray schedules .................................................................................................... 11 Paper IV. Nicotinamide as a repair inhibitor in vivo: single and fractionated X-ray dose studies in mouse skin and kidneys ................................. 11 Paper V. Acute and late morbidity in the treatment of advanced bladder cancer with accelerated radiotherapy, carbogen and nicotinamide ........................................................................... 12 Materials and methods ....................................................................................................................................... 13 Common methodology .............................................................................................................................. 13 Tumour studies .................................................................................................................................................. 13 Normal tissue studies .................................................................................................................................. 13 Models of early radiation damage .................................................................................................... 14 Models of late radiation damage ....................................................................................................... 14 Data analysis ........................................................................................................................................................ 15 Irradiation set up: x-ray treatments ................................................................................................. 15 Neutron treatments ....................................................................................................................................... 16 Nicotinamide pharmacokinetic studies ........................................................................................ 16