DOXORUBICIN INTERACTS DIRECTLY WITH SKINNED SINGLE SKELETAL-MUSCLE FIBERS

The effect of doxorubicin, a highly effective anticancer agent, on thc contractile apparatus of skinned single muscle fibres was tested in a concentration of 1-mu-M. Sarcomere length was set and held at 2-mu-m. Doxorubicin induced an increase in tension dependent on the Ca2+ concentration and time of incubation. The rise was up to 25% at [Ca2+] 40-mu-M. A parallel, small but significant shift of the calcium sensitivity curve, the relation between normalized tension and the negative logarithm of [Ca2+], the pCa, was observed. The results of this study suggest a direct interaction of doxorubicin with the actin myosin structure, possibly by an effect on myosin-ATP activity.