RESISTANCE OF HUMAN LARYNX-CARCINOMA CELLS TO CISPLATIN, GAMMA-IRRADIATION AND METHOTREXATE DOES NOT INVOLVE OVEREXPRESSION OF C-MYC OR C-KI-RAS ONCOGENES

In our previous study, we achieved resistance to cisplatin or vincrist ine (VCR) by repeated treatments of human larynx carcinoma HEp2 cells with these drugs. Resistant cells were cloned and four clones were sel ected: CA(3) and VA(3) clones were selected from cells acutely treated with cisplatin or VCR, while CK2 and VK2 cells were selected from cel ls chronically treated with cisplatin and VCR, respectively. The aim o f this study was to examine whether the development of resistance to c isplatin and vincristine changes the expression of c-myc and c-Ki-ras oncogenes and to determine whether there is a correlation between the expression of these oncogenes and the sensitivity of selected clones t o cisplatin, methotrexate and gamma-rays. The cell sensitivity to cisp latin, methotrexate and gamma-rays was determined on the basis of the clonogenic survival assay. The expression of c-myc and c-Ki-ras oncoge nes was examined by the use of RNA dot blot and Northern blot analyses . The results show that the development of resistance to selected drug s does not alter the expression of either c-myc or c-Ki-ras oncogene. CA(3) and CK2 clones were resistant to cisplatin, while the vincristin e resistant clones VA(3) and VK2 became sensitive to this drug. The se nsitivity of resistant clones to gamma-rays varied. CA(3) cells were r esistant, VA(3) and VK2 cells sensitive, while CK2 cells exhibited the same sensitivity to gamma-rays as did the parental cells. All four cl ones tested became cross-resistant to methotrexate. We can conclude th at development of resistance to cisplatin and vincristine does not alt er the expression of c-myc or c-Ki-ras oncogene. We did not find any c orrelation between expression of these oncogenes and the sensitivity t o cisplatin, methotrexate or gamma-rays.