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CELLULAR ANALYSIS AND DOSE-RESPONSE RELATIONSHIPS IN LONG TERM RADIATION INJURY TO MOUSE BONE MARROW, EPIDERMIS AND INTESTINE

Objective

STUDIES WILL BE MADE OF LONG-TERM INJURY IN HAEMOPOIETIC TISSUE. RADIATION DOSE/RESPONSE RELATIONSHIPS WILL BE INVESTIGATED, IN PARTICULAR WITH RESPECT TO THRESHOLD DOSES FOR STEM-CELL INJURY. THE DOSES WILL BE ACUTE, FRACTIONATED OR CHRONIC.
This study has greatly extended our knowledge of the radiation response of the haemopoietic system in different species, in particular concerning long term response and the effects of changing dose rate or fractionation patterns. A correlation is drawn between haemopoietic and stromal recovery, the latter being responsible for slow but extensive haemopoietic recovery after long very low dose rate irradiation.

Studies have greatly extended our knowledge of the radiation response of the haemopoietic system in different species, in particular concerning long term response and the effects of changing dose rate or fractionation patterns. A correlation is drawn between haemopoietic and stromal recovery, the latter being responsible for slow, but extensive, haemopoietic recovery after long very low dose rate irradiation.
IN MOUSE BONE MARROW, IT IS KNOWN THAT LARGE REPEATED DOSES OF RADIATION (4.5 GY X-RAYS) CAN LEAD TO A LONG-TERM DECLINE IN PERIPHERAL BLOOD CELLS (HENDRY ET AL, INT. J. RADIAT. ONCOL. BIOL. PHYS., 9, 164 (1983)). PERMANENT STEM-CELL INJURY CAN BE DETECTED AT EARLY TIMES, AND INCREASED NUMBERS OF DIVISIONS OF MATURING CELLS AND AN INCREASED RATE OF DIFFERENTIATION MAINTAINS THE BLOOD CELL COMPLEMENT FOR A FINITE PERIOD OF TIME. RECENTLY, IT HAS BEEN SHOWN THAT THESE DEFECTS ARE OBSERVED IN MICE ALSO AFTER DOSES LESS THAN 3 GY TOTAL DOSE. IT IS PROPOSED TO STUDY THE DOSE-RESPONSE CURVE AND THRESHOLD DOSES FOR THESE DEFECTS, ASSAYED AT VARIOUS TIMES UP TO 1 YEAR AFTER SINGLE, MULTIFRACTIONATED, REPEATED SINGLE, AND CHRONIC GAMMA-RAY EXPOSURES TO THE WHOLE BODY. ASSAYS WILL INCLUDE BLOOD COUNTS AND COLONY ASSAYS FOR HAEMOPOIETIC PROGENITOR CELLS E.G. STEM CELLS (CFU-S), GRANULOCYTIC (GM-CFC), AND ERYTHROID (BFU-E, CFU-E) PRECURSORS. CHANGES IN STIMULATING FACTORS KNOWN TO BE PRODUCED BY CELLS PRESENT IN THE BONE MARROW ALSO WILL BE MEASURED. ASSAYS FOR ENVIRONMENTAL INJURY WILL BE EMPLOYED E.G. FIBROBLASTOID PRECURSOR CELLS (CFU-F), TRANSPLANTED FEMORA, AND FEMORAL MARROW PLUGS TRANSPLANTED UNDER THE KIDNEY CAPSULE. ALSO, ASSAYS WILL BE DEVELOPED FOR QUANTIFYING ENDOTHELIAL CELL INJURY.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

Christie Hospital and Holt Radium Institute
Address
Wilmslow Road Withington
M20 9BX Manchester
United Kingdom