title: Induction of donor-type chimerism in murine recipients of bone marrow allografts by different radiation regimens currently used in treatment of leukemia patients.
abstract: Three radiation protocols currently used in treatment of leukemia patients before bone marrow transplantation (BMT) were investigated in a murine model (C57BL/6----C3H/HeJ) for BM allograft rejection. These include (a) a single dose of total body irradiation (8.5 Gy TBI delivered at a dose rate of 0.2 Gy/min), (b) fractionated TBI (12 Gy administered in six fractions, 2 Gy twice a day in 3 days, delivered at a dose rate of 0.1 Gy/min, and (c) hyperfractionated TBI (14.4 Gy administered in 12 fractions, 1.2 Gy three times a day in 3 days, delivered at a dose rate of 0.1 Gy/min). Donor-type chimerism 6 to 8 weeks after BMT and hematologic reconstitution on day 12 after BMT found in these groups were compared with results obtained in mice conditioned with 8 Gy TBI delivered at a dose rate of 0.67 Gy/min, routinely used in this murine model. The results in both parameters showed a marked advantage for the single dose 8.5 Gy TBI over all the other treatments. This advantage was found to be equivalent to three- to fourfold increment in the BM inoculum when compared with hyperfractionated radiation, which afforded the least favorable conditions for development of donor-type chimerism. The fractionated radiation protocol was equivalent in its efficacy to results obtained in mice irradiated by single-dose 8 Gy TBI, both of which afforded a smaller but not significant advantage over the hyperfractionated protocol. This model was also used to test the effect of radiation dose rate on the development of donor-type chimerism. A significant enhancement was found after an increase in dose rate from 0.1 to 0.7 Gy/min. Further enhancement could be achieved when the dose rate was increased to 1.3 Gy/min, but survival at this high dose rate was reduced. These results demonstrated indirectly that dose rate affects the expression of host-type pluripotent stem cells, the progeny of which appear 3 to 6 weeks after treatment with 8 Gy TBI delivered at a dose rate of 0.1 Gy/min, but which are eradicated if radiation is delivered at a dose rate of 1.3 Gy/min.
authors.affiliation: Department of Biophysics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: O
authors.initials: O
authors.lastname: Salomon
authors.forename: T
authors.initials: T
authors.lastname: Lapidot
authors.forename: A
authors.initials: A
authors.lastname: Terenzi
authors.forename: I
authors.initials: I
authors.lastname: Lubin
authors.forename: I
authors.initials: I
authors.lastname: Rabi
authors.forename: Y
authors.initials: Y
authors.lastname: Reisner
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000473:pathology; D005260:Female; D007942:Leukemia, Experimental / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D051379:Mice; D011828:Radiation Chimera; D013601:T-Lymphocytes / Q000473:pathology / Q000528:radiation effects; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation