PLASMA FL CONCENTRATION VARIATION AFTER HETEROGENEOUS IRRADIATION IN MICE.
Marie PRAT, Christelle DEMARQUAY, Johanna FRICK, Dominique THIERRY, Norbert-Claude GORIN, and Jean-Marc BERTHO, European Radiation Research 25-28/08/2004, Budapest, Hongrie.
Objective: We previously showed that plasma FL concentration was bio-indicator of the number of surviving progenitor both in the bone marrow and in the spleen after homogenous total body irradiation. In order to determine how FL can be used as a bio-indicator of heterogeneous bone marrow damage, we used a model of heterogeneous irradiated Balb/C mice. Methods: Mice were irradiated with 25%, 50%, 75% or 100% of bone marrow exposed to 4 Gy, 8 Gy, or 12 Gy of gamma rays (60Cobalt). Twice a week during four weeks, 5 mice of each configuration were euthanasied and blood cell count, formula, plasma FL concentration, exposed and non exposed bone marrow Colony Forming Cells (CFC) and spleen CFC were defined. Results: An early decrease in WBC numbers was observed after irradiation whatever the dose and the configuration. This decrease and the recovery were dose dependent and depended on the size of the exposed medullar territory. Results also showed an increase in plasma FL concentration after irradiation whatever the dose and the configuration. In fact, the plasma FL concentration increased with the dose and the size of the exposed medullar territory. As for WBC, a decrease in absolute CFC numbers that depends on the irradiation dose and the size of the exposed medullar territory was observed in exposed bone marrow. By contrast, in unexposed bone marrow as in spleen (not exposed) results indicates that the absolute CFC numbers could decrease after irradiation. These results suggest a modification of the hematopoietic progenitor distribution after irradiation. We then correlated the total CFC numbers in mice (ie irradiated bone marrow CFC plus non exposed bone marrow CFC plus spleen CFC) to the plasma FL concentration. Results demonstrate that plasma FL concentration was negatively correlated to the total CFC numbers whatever the dose and the percentage of exposed bone marrow. Conclusion: These results demonstrate that plasma FL concentration reflect the number of residual CFC in mice after irradiation whatever the dose, the size of the exposed medullar territory and the time after irradiation. It thus reflects the total bone marrow damage and the ability of hematopoietic recovery. This bio-indicator would be useful both in accidental irradiation situations to help in the therapeutic choice and in the follow-up of the radiotherapy patient.