engleski

Low doses of gamma rays: molecular alterations induced in tumor cells

We have shown previously, that human cervical carcinoma cells irradiated with low doses of gamma rays (0.5 Gy x 30 fractions ; HeLa1500 cells), changed their sensitivity to the subsequent treatment with various structurally and functionally unrelated anticancer drugs (1). Several possible mechanisms were examined that could explain the drug-resistance of preirradiated cells (2, 3). However, the determined alterations were not sufficient to explain the level of drug-resistance. Therefore, the aim of the present study was to investigate further molecular mechanisms that are involved in this phenomenon. The interest was focused on the genes involved in the repair of DNA damage and apoptosis. The expression of corresponding genes was analysed by Western blot method. The kinetic of apoptosis was followed under the fluorescent microscope. The activity of caspases was determined by a commercial kit. Our results show that the constitutive levels of the proteins involved in mismatch repair, as well as ERCC1, were not altered in HeLa1500 cells. The induction of apoptosis (following the treatment with cisplatin) was inhibited in HeLa1500 cells. Preliminary results show that in HeLa1500 cells (as compared to control cells), the expression of BCL-2 was increased, the expression of caspases was altered. In conclusion, low doses of gamma rays may change the sensitivity of irradiated cells to the subsequent treatment with drugs due to the inhibition of apoptosis. References 1. Osmak M., Perović S., Int. J. Radiat. Oncol. Biol. Phys., 16 (1989) 1537-1541. 2 . Osmak M., Neoplasma, 40 (1993) 97-101. 3. Osmak M., Matulić M., Sorić J., Neoplasma, 40(1993) 359-362.

low doses; ionising radiation; human cells; apoptosis

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