Hematoporphyrin derivative rescue from toxicity caused by chemotherapy or radiation in a murine leukemia model (L1210).
Hematoporphyrin [1,3,5,8-tetramethyl-2,4-bis(hydroxyethyl)-porphin-6,7-dipropio nic acid dihydrochloride derivative] (HPD) is a compound that was studied in a number of laboratories because of its cytocidal activity after activation by light. Modification of immune function seen during the photochemotherapeutic studies prompted attempts to determine the effect of HPD on the immune and hemopoietic systems. Splenic hyperplasia as well as marrow hypercellularity were noted in mice treated with HPD. In vitro phytohemagglutinin or lipopolysaccharide stimulation of spleen lymphocytes caused normal or scant increases in blast transformation compared to the stimulation index for lymphocytes from untreated animals. HPD treatment did not significantly alter production of antibody to sheep red blood cells, as evaluated by hemagglutination or hemolytic assay. In contrast, HPD treatment did promote an increased number of spleen colonies in lethally irradiated mice transfused with syngeneic bone marrow. The capacity of HPD to increase the number of bone marrow and spleen cells has been exploited to accelerate the recovery from peripheral leukopenia induced in animals by previous drug or radiation treatment. The time for full return from severe leukopenia induced by an antimetabolite compound (5-fluorouracil) or an alkylating agent (cyclophosphamide or X-rays was significantly shorter in mice treated with HPD than in controls. Furthermore, improved survival was demonstrated in irradiated mice after HPD treatment. Finally, HPD treatment of L1210 leukemic mice did not affect the antitumor activity of cyclophosphamide. If the properties described here be confirmed, HPD might contribute to recovery of leukopenic cancer patients.
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000633:toxicity*; D005472:Fluorouracil / Q000633:toxicity*; D006384:Hemagglutination / Q000187:drug effects; D017324:Hematoporphyrin Derivative; D006415:Hematoporphyrins / Q000627:therapeutic use*; D006461:Hemolysis / Q000187:drug effects; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000532:radiotherapy*; D007962:Leukocytes / Q000528:radiation effects; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011878:Radiotherapy / Q000009:adverse effects
D000970:Antineoplastic Agents; D006415:Hematoporphyrins; D017324:Hematoporphyrin Derivative; D003520:Cyclophosphamide; D005472:Fluorouracil