The paradoxes in patterns and mechanism of bone marrow regeneration after irradiation. 1. Different volumes and doses.
Bone marrow regeneration (BMR) following irradiation has been largely studied as a dose-effect phenomenon, however, a large literature has simultaneously developed utilizing a wide variety of volumes, both in clinical studies and in experimental studies. In human situations radiation treatment fields and the amount of bone marrow organ exposed have ranged from total body irradiation (small daily and total doses) to large field (half-body) single high doses encompassing 50% of the bone marrow, to segmental or localized field (50-25%). Volume factors, more than dose, determine patterns of suppression and regeneration which have been documented by a variety of assay systems. Experimental evidence is presented which indicates that high dose irradiation (500-1000 cGy) to large volumes of bone marrow (50%) does not completely suppress bone marrow regeneration but results in a rapid compensatory response. The nadir response of bone marrow CFUc-GM stem cell compartment was directly proportional to increasing doses of irradiation (200-2000 cGy) delivered to a single limb. Immediate depression of CFUc-GM was followed by an increase proliferative phase with the most notable difference observed in doses less than or greater than 1000 rad. Following doses of 500 and 1000 rad to large field (half-body), an immediate depression was again observed followed by an immediate and greater compensatory response particularly after the 1000 rad dose. Comparisons ae made between the small and larger volumes at similar doses and indicate a greater overall compensatory response after the larger field irradiation, being more rapid in onset particularly after the 1000 rad dose. Although in-field regeneration of bone marrow occurs after single dose radiation to different volumes of bone marrow, experimental and clinical evidence from protracted conventional doses of irradiation to different volumes of bone marrow (greater or less than 50%) indicate significantly different response mechanisms. From our laboratory and clinical investigations it can be determined that bone marrow is extremely sensitive to radiation insult and has different compensatory mechanisms to "fine tune" its response in proportion to the volume insulted.
D000818:Animals; D001853:Bone Marrow / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006412:Hematopoietic Stem Cells / Q000528:radiation effects; D011817:Rabbits; D012038:Regeneration; D013997:Time Factors