Investigation of acute myelosuppressive effect of dacarbazine on experimental model

Boris Milijasevic1, Dusan Stefanovic2, Dusan Lalosevic3, Momir Mikov1, Zdenko Tomic1, Ana Sabo1, Jovanka Kolarovic4. 1Faculty of Medicine, University of Novi Sad, Department of Pharmacology, toxicology and clinical pharmacology, Serbia, 2Faculty of Medicine, University of Novi Sad, Department of Pathology, Serbia, 3Faculty of Medicine, University of Novi Sad, Department of Histology and Embryology, Serbia, 4Faculty of Medicine, University of Novi Sad, Department of Pediatrics, Serbia

Introduction: The therapy of soft-tissue sarcomas usually involves Dacarbazine – an alkylating agent which works by methylation of DNA and inhibition of synthesis of purines and RNA. Side effects of Dacarbazine therapy include gastrointestinal, liver and kidney problems, and severe myelosuppression. The precise acute hematological changes caused by single dose of Dacarbazine aren’t described in available literature.

Objective: The aim of our experiment was to study acute hematologic changes caused by Dacarbazine on hamsters with previously induced fibrosarcoma.

Materials and methods: We used one control and four experimental groups of Golden Syrian hamsters. On the 1st day of experiment they were given trypsinized cells from Baby Hamster Kidney (BHK) culture subcutaneously, which are tumorogenes for Syrian hamsters. On the 14th day the experimental groups had received different doses of Dacarbazine by intraperitoneal injection: 1.200, 1.400, 1.600 and 2.000 mg/m2. Seven days later all hamsters were sacrificed by ether anesthesia and their blood samples were collected for further analysis. We used Neubauer’s chamber and appropriate reagents (Türk, Hayem and Dacie) in order to count leukocytes, erythrocytes and thrombocytes. Blood samples were also stained with brilliant cresyl blue and Giemsa in order to count reticulocytes and to differ leukocytes.

Results: Induced fibrosarcoma per se caused anaemia, thrombocytopenia and contrary to previously, leukocytosis, which was mainly based on neutrophilia and monocytosis. Experimental groups had shown anaemia, thrombocytopenia and leukopenia, which was basically only lymphocytopenia, but all other leukocytes were close to lower referent level. The numbers of all blood cell types were lowered in proportion to Dacarbazine doze. Reticulocytes had vanished from blood when maximum dose of Dacarbazine had been used.

Conclusion: Dacarbazine has powerful general myelosuppressive effect, but lymphocytes and erythrocytes are mostly affected. The single dose of 2.000 mg/m2 induces complete suppression of red bloodline in hamsters.

Keywords: Dacarbazine, haematology, fibrosarcoma, cytostatic drug.

This research was financially supported by Ministry of Science, Republic of Serbia, project no 41012.