Cross resistance and cellular uptake of 4'-O-methyldoxorubicin in experimental tumors with acquired resistance to doxorubicin.
A new analog of doxorubicin, 4'-O-methyldoxorubicin, was previously reported to have a pronounced activity against L1210 leukemia, which shows a natural partial resistance to doxorubicin itself. In the present study, lines of P388 leukemia and Ehrlich ascites tumor with acquired resistance to doxorubicin were found to be cross-resistant to 4'-O-methyldoxorubicin, indicating that the natural and the acquired resistance to doxorubicin involve different mechanisms. In vitro studies on the uptake of 4'-O-methyldoxorubicin in the Ehrlich ascites tumor cells indicated that the observed cross-resistance was partly due to a decreased drug uptake in the resistant cells because of an increased extrusion of the drug, in accordance with previous findings on the mechanism of acquired resistance to doxorubicin.
D000042:Absorption; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism* / Q000473:pathology; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D004351:Drug Resistance; D007941:Leukemia P388 / Q000378:metabolism* / Q000473:pathology; D007942:Leukemia, Experimental / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; C030772:4'-O-methyldoxorubicin; D004317:Doxorubicin