[en] We previously found that human cervix carcinoma HeLa cell irradiated with multiple fractions of gamma rays (0.5 Gy daily, five times per week over 6 weeks) become resistant to cis--dichlorodiammine platinum(II) (cis-DDP), methotrexate (MTX) and vincristine (VCR), but retain the same sensitivity to gamma rays or UV light. In the present report attempts were made to elucidate the mechanisms by which these these cells have acquired resistance to cis-DDP and VCR. The sensitivity to different drugs was measured by modified MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)method. Neither buthionine sulfoximine (BSO) nor ethacrinic acid were able to reverse the resistance of preirradiated cells to cis_DDP. Therefore, neither the increased levels of glutathione nor glutathione transferase seem to be involved in resistance to cis-DDP. Resistance of preirradiated cells to vincristine was abolished by the addition of verapamil, indicating that resistance to this drug may depend on the increased expression of plasma membrane P-glycoprotein. It was concluded that mechanism of resistance of preirradiated cells to cytostatics are multi-factorial and involve at least the increased levels of metallothioneins and changes in the plasma membrane. Acquired resistance to cytotoxic drugs induced by preirradiation may be the reason for the induced response to these drugs after radiation treatment of certain tumors. (author)