Amifostine does not inhibit the toxic effects of Anthracycline derivates or Mitoxantrone on MDR tumor cell lines

In this work three human cell lines with multidrug resistance (MDR) caused by a P-glycoprotein (PGP) overexpression, CEM VLB, HL60 DNR. LOVO DX and tw o cell lines with MDR associated with a multidrug related protein (MRP) or a lung resistance-related protein (LRP) overexpression named GLC4 ADR and S W1573/2R120 were tested for Amifostine protection against Daunorubicin, Dox orubicin, Idarubicin and Mitoxantrone toxicity. This class of anticancer ag ents was chosen because they are commonly used in the first line treatments of acute leukemias where a PGP, an LRP or an MRP overexpression often occu rs even at onset. A 7-day incubation with escalating doses of anticancer ag ents with or without a 15 minute preincubation in Amifostine or its active metabolite WR-1065 were used. In conclusion, in none of the MDR positive an d negative cell lines did Amifostine modify the toxicity of the anticancer drugs. The observation that even the WR-1065 metabolite gave no protection against Anthracyclines toxicity strengthened the data and provided confirma tion for the further in vivo testing of the safety and efficacy of Amifosti ne in leukemias.