COMPROMISING EFFECT OF LOW DOSE-RATE TOTAL-BODY IRRADIATION ON ALLOGENEIC BONE-MARROW ENGRAFTMENT

Citation
R. Vanos et al., COMPROMISING EFFECT OF LOW DOSE-RATE TOTAL-BODY IRRADIATION ON ALLOGENEIC BONE-MARROW ENGRAFTMENT, International journal of radiation biology, 64(6), 1993, pp. 761-770
Citations number
43
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Radiology,Nuclear Medicine & Medical Imaging","Nuclear Sciences & Tecnology
ISSN journal
0955-3002
Volume
64
Issue
6
Year of publication
1993
Pages
761 - 770
Database
ISI
SICI code
0955-3002(1993)64:6<761:CEOLDT>2.0.ZU;2-#
Abstract
The protraction of total body irradiation (TBI) to a continuous low do se-rate has been investigated for its effect on donor marrow engraftme nt in murine bone marrow transplant (BMT) models of varying histocompa tibility. Three different BMT combinations were used: syngeneic [B6-Gp i-1a --> B6-Gpi-1b], H-2 compatible allogeneic [BALB.B (H-2b) --> B6 ( H-2b)] and H-2 mismatched allogeneic [BALB/c (H-2d) --> B6 (H-2b)]. TB I was delivered over a range of doses at either a high (HDR, 40 cGy/mi n) or low (LDR, 2 cGy/min) dose rate followed by infusion of 10(7) bon e marrow cells from syngeneic or allogeneic donors. The level of donor (Gpi-1a) engraftment was determined from blood Gpi-typing at differen t times after TBI and BMT. Radiation dose-response relationships corre sponding to long-term haemopoietic engraftment at 20 weeks showed a do se-sparing effect of LDR that became more prominent with increasing ge netic disparity between donor and host. For fully allogeneic (H-2 inco mpatible) BMT, a dose as high as 16 Gy LDR was still not sufficient fo r achieving chimerism in all recipients. In many cases allogeneic BMT gave transient blood chimerism enabling the recipient to survive the a cute effects of high dose TBI with full long-term repopulation from su rviving stem cells of the host. Radiation cell survival curves were ob tained for the frequency of alloreactive precursors of proliferating T -lymphocytes (pPTL) remaining in the spleen at 1 day after TBI. A radi ation dose-sparing effect of LDR was also found for pPTL depletion. Th ese data suggest that radiation damage repair during LDR irradiation i n an immunocyte target cell population is mainly responsible for enhan ced graft rejection thus rendering protracted TBI less effective for a pplication in clinical allogeneic BMT.