Sensitivity to anthracyclines in P388/dx leukaemia cells

It has been demonstrated previously that neoplastic cells with reduced oxygen consumption are more sensitive to doxorubicin8. We have examined the relationship between doxorubicin sensitivity and oxygen consumption of P388 murine leukaemia cell line (P388) and of a doxorubicin resistant subline (P388/dx). Oxygen utilization by P388/dx cells was higher than that found in the sensitive line. A variety of calcium antagonists, including channel blockers and intracellular antagonists (verapamil, trifluoperazine, dantrolene, TMB-8, nitrendipine) or membrane acting drugs (lucensomycin), enhanced the cytotoxic activity of doxorubicin in P388 and markedly in P388/dx subline. This action was accompanied by a reduction of oxygen consumption more pronounced in the resistant cells. These findings emphasizé the correlation between oxygen uptake, instead of calcium dependent processes, and doxorubicin responsiveness. The calcium ionophores A 23187 failed to alter doxorubicin activity in P388 and P388/dx leukaemia.