Reduction of hematotoxicity and augmentation of antitumor efficacy of cyclophosphamide by dopamine.
Modulatory effects of dopamine (DA) on hematotoxicity and antitumor efficacy of cyclophosphamide (CY) were studied in Swiss mice bearing transplantable Ehrlich ascites carcinoma (EAC). DA was administered i.p. at a dose of 50 mg/kg/day for 5 consecutive days beginning day 3 after tumor transplantation. CY (200 mg/kg i.p.) was injected 24 hour after completion of DA treatment. DA pretreatment reduced the suppressive effects of CY on hemoglobin, RBC, total WBC, neutrophil, platelet, and bone marrow nucleated cell counts. Likewise, DA partially prevented the CY-induced fall in pluripotent (CFU-S12) and lineage-specific stem cells for granulocytes (CFU-C) in bone marrow. Moreover, mice receiving a combination of DA and CY illustrated greater reduction in tumor volume, viable tumor cell count and mitotic index along with upregulation of tumor cell apoptosis than CY-only group. As a result, the former group demonstrated prolonged hosts survival. Thus, DA protected to a great extent the hematopoietic cells of tumor bearing hosts from the suppressive action of CY and concomitantly augmented its antitumor efficacy resulting in improved hosts survival.
Lakshmi
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Experimental Hematology Unit, Chittaranjan National Cancer Institute, Kolkata 700026, India.
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Ray
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D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects* / Q000494:pharmacology*; D017209:Apoptosis; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D049109:Cell Proliferation; D002470:Cell Survival; D003520:Cyclophosphamide / Q000009:adverse effects* / Q000494:pharmacology*; D004298:Dopamine / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008940:Mitotic Index; D016019:Survival Analysis; D015854:Up-Regulation
D018906:Antineoplastic Agents, Alkylating; D002316:Cardiotonic Agents; D003520:Cyclophosphamide; D004298:Dopamine