engleski

THE ASSESSMENT OF BLEOMYCIN AND MITOMYCIN C TOXICITY ON HUMAN PERIPHERAL BLOOD LYMPHOCYTES USING THE ALKALINE COMET ASSAY

Chemotherapy is frequently used in the adjuvant setting following surgical removal of the primary tumor in cancer patients. Although therapeutic efforts are directed toward cancer tissue, the DNA of non-cancer cells is also subjected to damage during chemotherapy. The correlation between exposure of cancer patients to antineoplastic drugs and alterations of DNA repair efficiency is usually studied on different surogate cells, such as peripheral blood lymphocytes. The aim of present study was to evaluate the genotoxic potential of two antineoplastic drugs: bleomycin and mitomycin C on human peripheral lymphocytes. Both drugs are potent cytotoxic antibiotic involved in many standard chemotherapy regimens used in adjuvant chemotherapy of various human cancers. Genotoxic efectiveness of above mentioned cytostatics was evaluated following 24-hour in vitro treatments of human blood samples with their therapeutic concentrations (15 mg/m2 of bleomycin and 12 mg/m2 of mitomycin C). Single antineoplastic drugs and their combination were added into the blood cultures at the onset of the cell cultures or 24 hours after lymphocytes were grown in vitro. As a sensitive biomarker for the assessment of DNA damage the alkaline comet assay was selected. The levels of DNA damage and repair were evaluated immediately after treatment as well as 24 and 48 hours following treatment. The results show that both drugs in their therapeutic concentrations induce significant DNA damage to peripheral blood lymphocytes. The dynamic of the DNA damage infliction and repair was dependent on their genotoxic mechanisms. Bleomycin has induced the highest level of DNA damage immediately after treatment. On the other hand, the increased levels of DNA damage in mitomycin C-treated cells were detected during the recovery period. Similar levels of DNA damage could be also expected in non-cancer cells of patients who received chemotherapy. Although the primary DNA damage is subjected to efficient repair processes, some alterations remain persistant. It was observed that genetic damage caused by the chemotherapeutic treatment in many cancer patients contribute to the development of secondary malignancies unrelated to the original neoplasia. As sensitive predictors, certain biological markers, such as the alkaline comet assay, could allow us to detect and identify sensitive subpopulations with increased genotoxic risks.

lymphocytes; bleomycin; mitomycin C; comet assay

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