Royal academy of medicine in ireland section of biomedical sciences

The response of normal tissues is a major limiting factor when radiotherapy and chemotherapy are combined. Improved antitumour responses found in combined treatments have often been accompanied by an attendant increase in normal tissue damage within the radiation field and thus there has been no increase in therapeutic ratio. This may not occur when radiation is combined with bioreductive drugs since these agents should not be metabolised in well-oxygenated normal tissues and therefore should not exacerbate normal tissue damage. To investigate this hypothesis we have studied eccrine sweat gland function 1 in two strains of mice following irradiation of the dorsal surface of the right hind foot. On several occasions post irradiation (range 126 weeks) sweating was stimulated by intraperitoneal injection of pilocarpine (0.05% in phosphate buffered saline). Ten minutes later casts of both hind feet were made using a silicone elastomer. The setting of the cast was inhibited over functional sweat glands. The final cast therefore could be used as a permanent record of the extent of sweat gland function. Results showed that the response was similar, although not identical, in two different strains of male mice 9CBA and B6D2FI) with a dose dependent nadir of function in the irradiated foot as compared to the unirradiated hind foot at about 8 weeks post treatment (<50% loss at 8.5 Gy). Partial function did return to a plateau by 26 weeks but some residual damage remained which was greater the higher the initial dose of irradiation. In conclusion this assay provides a reproducible and quantifiable assay of radiation damage to a late reacting tissue in the mouse and it is now being used to evaluate normal tissue response to combined modality treatment. Reference I. Joiner, M. C., Johns, H. A new assay for the functional response of