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PARENT SESSION
1:30 PM to 3:30 PM
Sunday, April 21, 2002
Poster Session 2 High LET Effects

Room: Nevada Exhibition Center

(P07-54) Comparison of immunomodulatory effects in strains of mice differing in susceptibility to high linear energy transfer (LET) radiation.

Gridley, Daila*,1, Pecaut, Michael1, Nelson, Gregory1, 1 Chan Shun Pavilion, Room A-1010, Loma Linda, CA

ABSTRACT-
Although radiation can result in immunodepression and increased risk for cancer, genetic background is an important factor in the outcome. C57BL/6 and CBA/Ca mice are resistant and susceptible, respectively, to radiation-induced genomic instability and develop different tumor types after exposure to high LET radiation. In the present study, C57BL/6 (n=60) and CBA/Ca (n=59) mice were exposed to 0, 0.5, 2.0 and 3.0 gray (Gy) total doses of whole-body heavy iron ion (56-Fe, Z=26, ~1Gy/min) irradiation using the Alternative Gradient Synchrotron at Brookhaven National Laboratory. Subsets from each group were euthanized on days 4 and 30 thereafter for assay. Three-way analysis of variance, using radiation dose, day, and mouse strain as the independent variables, indicated there were significant main effects of all three variables in a number of endpoints, including body and spleen mass, monocyte count and percentage, red blood cell (RBC) count, hematocrit (HCT), platelet number and volume, and splenocyte response to two different T lymphocyte mitogens (phytohemagglutinin, PHA and concanavalin A, ConA) (p<0.05). A number of interactive effects were also noted. For example, radiation dose x strain (p<0.01) and day x strain (p<0.05) interactions were found in the response to ConA, which was low in irradiated C57 but normal in irradiated CBA mice on day 30. The WBC count in C57 mice was above non-irradiated controls, whereas in CBA mice the means were below non-irradiated controls (day x strain, p<0.0001). Furthermore, there were dose x day x strain interactions in a number of parameters, including circulating monocyte percentage, mean platelet volume, RBC count, HCT, and hemoglobin concentration (p<0.05). This appeared to be due to dose-dependent changes in all of these parameters in the C57 mice on day 4. Such dramatic dose dependencies were not consistently seen in the CBA mice. Collectively, the data indicate that the degree and pattern of lymphoid tissue susceptibility, and possibly also hematopoietic reconstitution, after high-LET radiation are different in these two strains. Studies are underway in our laboratory to determine if these differences play a role in the types of tumors that appear after radiation exposure. Supported by NASA Coop. Agreement NCC9-79 and the Chan Shun International Foundation.

KEYWORDS: immunomodulation, lymphoid tissues, genetic background, erythrocytes