The protection of hemopoietic mice progenitors by WR-2721 during photodynamic therapy.
Photodynamic therapy is a new concept for in vitro evaluation of bone marrow clearance in leukemia. This treatment eliminates 99.9999% of leukemic cells, but under the same conditions over 50% of normal bone marrow cells are damaged. WR-2721, a thiol compound, is reported to except a protective effect for bone marrow against radiation therapy. This study analyzed the protective effect of WR-2721 during photodynamic therapy with hematoporphyrin derivative. Mice hemopoietic cells were exposed to laser light after sensitization by hematoporphyrin, with or without WR-2721 at 3 dose levels (250, 500, 750 mg/kg). The efficacy of protection was evaluated by GM-CFU assay in collagen gel medium. Results showed significant protection at 25 and 50 j/cm2 (p less than 0.05), but at 75 j/cm2 irradiation only the 750 mg/kg dosage remained protective. The protective factor of WR-2721 is 1.65 (95% confidence interval: 1.38-1.99) WR-2721 is protective against photodynamic lesions but this protection is diminished by increased irradiation energy. The best results are obtained with a dose of 750 mg/kg though this appears to be toxic. Further studies are needed to evaluate the action of WR-2721 on leukemic cells before the use of WR-2721 in bone marrow clearance.
Maloisel
F
F
Institut d'Hématologie, Hospices Civils, Strasbourg, France.
Foultier
M T
MT
Patrice
T
T
Praloran
V
V
Oberling
F
F
Le Bodic
L
L
D004999:Amifostine / Q000627:therapeutic use*; D000818:Animals; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D010778:Photochemotherapy / Q000379:methods*
D004999:Amifostine