Effect of porphyrins on the hematopoietic recovery of mice treated with gamma-radiation.
Porphyrins are a group of organic compounds involved in a wide spectrum of fundamental biological processes. Non-metallic, naturally occurring and synthetic porphyrin derivatives may produce cytotoxic effects in malignant or normal tissues exposed to visible light. Supra-clinical doses of the photosensitizing porphyrin, Photofrin are hematostimulatory when administered to normal and immunosuppressed inbred mice. To determine if a non-photosensitizing metalloporphyrin has similar hematostimulatory activity, we have synthesized iron (III) hematoporphyrin chloride (FeHp) and administered it to sub-lethally irradiated mice. FeHp (10 mg/kg) given 1 and 4 days or 1, 4 and 7 days following sub-lethal (7 Gy) whole body irradiation significantly increased spleen colony forming units of progenitor cells of the granulocyte-macrophage lineage (CFU-GM) 14 days post-irradiation, relative to irradiated controls. In addition, total splenocyte numbers were significantly increased 17 days post-irradiation in mice that had received FeHp 1 and 4 days post-irradiation. When FeHp was given 24 hours prior to irradiation and again 48 hours or 48 and 96 hours post-irradiation, significant increases in splenic CFU-GM and spleen cell numbers, relative to control mice, were observed 15 days post-irradiation. A non-metallic photosensitizing monomeric fraction of Photofrin, deuteroporphyrin IX, 2,4 (4,2) hydroxyethyl vinyl (HVD) was compared to Photofrin for its ability to influence the hematopoietic recovery of irradiated mice. Only Photofrin but not HVD given in 3 doses (10 mg/kg) 1, 4 and 7 days following irradiation (4.8 Gy) significantly enhanced the recovery of spleen cellularity and splenic CFU-GM. In addition, Photofrin significantly increased bone marrow CFU-GM 7 and 10 days following the sub-lethal dose of gamma-radiation. The mechanism by which certain porphyrins augment hematopoiesis in the mouse is unknown. However, the identification of FeHp as a non-photosensitizing monomeric porphyrin with hematostimulatory activity in vivo, indicates that further study of metalloporphyrins is warranted and may reveal their clinical potential within the context of therapeutically-induced immunosuppression.
Hunt
D W
DW
Department of Microbiology, University of British Columbia, Vancouver, Canada.
Sorrenti
R A
RA
Renke
M E
ME
Xie
L Y
LY
Waterfield
E M
EM
Levy
J G
JG
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000528:radiation effects; D001854:Bone Marrow Cells; D003114:Colony-Forming Units Assay; D003905:Deuteroporphyrins / Q000494:pharmacology*; D017323:Dihematoporphyrin Ether / Q000494:pharmacology; D005720:Gamma Rays; D006410:Hematopoiesis / Q000187:drug effects* / Q000528:radiation effects*; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology*; D051379:Mice; D008811:Mice, Inbred DBA; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects
D003905:Deuteroporphyrins; D008665:Metalloporphyrins; C015213:ferric porphine complex; C049889:hydroxyethylvinyldeuteroporphyrin; D017323:Dihematoporphyrin Ether