engleski

Cell respose to repeated doses of ionising radiation: inhibition of apoptosis in cisplatin treated human cells

Background and purpose: Human cervical carcinoma HeLa cells exposed to low repeated doses of ionising radiation altered their response to cytostatics. The aim of the present study was to determine the molecular mechanisms involved in the resistance of preirradiated cells to cisplatin. Materials and methods: The profile of cytosolic proteins was examined for control and preirradiated HeLa cells by SDS-electrophoresis. The kinetics of apoptosis was followed by fluorescent microscope in control HeLa and preirradiated HeLa cells during 72 hours after 1 hour cell treatment with 50 or 150 microM cisplatin. Analysid of DNA fragmentation was done by agarose gel electrophoresis. Results: SDS-electrophoresis of the cytosolic proteins from parental HeLa and preirradiated HeLa 1500 cells exibited a similar pattern. The number of apoptotic cells increased during the posttreatment period. A higher dose of cisplatin induced more apoptotic cells than lower cisplatin dose. For both doses, however, significantly lower number of apoptotic cells was determined in preirradiated than in control cells. The nucleosome ladder was observed in human cervical carcinoma cells 12 hours after the cisplatin treatment. Conclusions: Our in vitro studies indicate that repeated low dose irradiation can induce drug resistance in the cells due to the same mechanisms that are involved in the resistance development induced by cytostatics. Inhibition of apoptosis may be one of them.

gamma irradiation; cell cultures; drug-resistance; apoptosis

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