Accelerated myelopoietic recovery in irradiated mice treated with Photofrin.
The porphyrin photosensitizer, Photofrin porfimer sodium (Photofrin), has been widely studied for its capacity to evoke destruction of malignant tissues. In addition to its photosensitizing properties, Photofrin may exert myelostimulatory effects in normal and immunosuppressed mice in the absence of activating light. In the present set of experiments, we examined the effect of Photofrin upon the immunohematopoietic axis of sublethally irradiated DBA/2 mice. Administration of Photofrin (10 mg/kg) 1 and 4 days following irradiation (4 Gy) significantly enhanced the recovery of spleen cellularity, spleen and bone granulocyte/macrophage progenitors (colony-forming units, CFU-GM) and peripheral blood leukocytes levels. Proliferative responses to the T-cell mitogen concanavalin A by spleen cells prepared from Photofrin-treated mice were significantly less than those of cells from irradiated control mice 8 and 15 days post-irradiation. Photofrin given 1, 4 and 7 days following irradiation elevated splenic CFU-GM 3 to 4-fold 10 days post-irradiation relative to the irradiated controls and mice given only two injections of Photofrin. In contrast to the effect of two injections, multiple (three or four) injections of Photofrin did not elevate bone marrow CFU-GM above control levels beyond 8 days post-irradiation. In addition, splenic CFU-GM levels in animals receiving three or four injections of Photofrin were no different than those of the irradiated controls later than 10 days post-irradiation. These findings indicate that prolonged exposure to Photofrin in sublethally irradiated mice may induce regulatory factors which dampen the enhanced myelopoietic recovery stimulated by only two injections of the drug.
Hunt
D W
DW
Department of Microbiology and Immunology, University of British Columbia, Canada.
Sorrenti
R A
RA
Renke
M E
ME
Waterfield
E
E
Levy
J G
JG
D000818:Animals; D003114:Colony-Forming Units Assay; D006410:Hematopoiesis / Q000187:drug effects*; D017324:Hematoporphyrin Derivative / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008934:Mitogens / Q000494:pharmacology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011833:Radiation Injuries, Experimental / Q000188:drug therapy*; D014916:Whole-Body Irradiation
D008934:Mitogens; D017319:Photosensitizing Agents; D017324:Hematoporphyrin Derivative