TRANSFORMATION BY V-RAS ONCOGENE CORRELATES WITH AN INCREASED DRUG-RESISTANCE IN AN EPITHELIAL THYROID-CELL SYSTEM

The effects exerted by ms transformation upon sensitivity to anticance r drugs by using an epithelial cell system displaying different levels of ras expression which well correlate with different degrees of cell malignancy have been evaluated. The diminished drug accumulation of t he transformed cell lines was found to be correlated with a depolariza tion of the cell membrane as observed by a flow cytometric analysis an d not correlated with the multidrug resistance (mdr) protein. The most resistant cell line, MPTK-6, showed the lowest drug accumulation leve ls and the lowest membrane potential. These observations indicate that ras neoplastic transformation of the rat thyroid epithelial cells mod ifies the membrane potential and this modification is possibly involve d in anticancer drugs resistance.