Morphological changes of vital organs and tumor in dacarbazine single dose use – an experimental model

Dusan Lalosevic1, Dusan Stefanovic2, Boris Milijasevic3, Momir Mikov3, Zdenko Tomic3, Ana Sabo3, Jovanka Kolarovic4. 1Faculty of Medicine, University of Novi Sad, Department of Histology and Embryology, Serbia, 2Faculty of Medicine, University of Novi Sad, Department of Pathology, Serbia, 3Faculty of Medicine, University of Novi Sad, Department of Pharmacology, toxicology and clinical pharmacology, Serbia, 4Faculty of Medicine, University of Novi Sad, Department of Pediatrics, Serbia

Introduction: Dacarbazine is widely used cytostatic drug in monotherapy or adjuvant therapy of soft tissue sarcomas. It works by methylation of DNA and inhibition of synthesis of RNA, purines and proteins. Side effects of Dacarbazine therapy include gastrointestinal, liver and kidney problems, myelosuppression and pneumonia. The precise histological changes that occur during Dacarbazine treatment of a sarcoma aren’t described in available literature.

Objective: The aim of our experiment was to study acute histological 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 heart, lung, liver, kidney, small intestine, spleen and tumor samples were proceeded. Tissue samples were fixed in buffered formalin, dehydrated with ethanol and xylene, embedded in paraffin, cut on microtome and stained with H&E. We used special ocular accessory with engraved chamber to count mitoses in tumor.

Results: Dacarbazine caused mild hepatitis: parenchymal degeneration of hepatocytes with portal mixed inflammatory infiltrates and foci of inflammatory cells inside liver lobules. There were no significant morphological changes on other proceeded organs. Tumor samples showed “ballooning degeneration of nuclei” which was manifested by enlargement of nucleus, pale nucleoplasma and lowered number of enlarged nucleoli. Number of mitosis in tumor was lowered in proportion to Dacarbazine doze.

Conclusion: Mild hepatitis and “ballooning degeneration of nuclei” of tumor cells were main morphological features of acute organotoxic and tumorotoxic effect of Dacarbazine single doze.

Keywords: Dacarbazine, histology, fibrosarcoma, cytostatic drug.

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