INVIVO CHARACTERISTICS OF RESISTANCE AND CROSS-RESISTANCE OF AN ADRIAMYCIN-RESISTANT SUBLINE OF P388 LEUKEMIA

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  • 1 January 1978
    • journal article
    • research article
    • Vol. 62  (10) , 1535-1547
Abstract
A subline of [mouse] P388 leukemia resistant to adriamycin (P388/ADR) was developed by exposure to the drug in vivo. Resistance to adriamycin was a stable characteristic of P388/ADR. There was no significant inhibition of nucleic acid synthesis in P388/ADR cells in vivo following a dose of 10 mg/kg of adriamycin, there was a prolonged and complete inhibition, particularly of DNA synthesis, in parental sensitive P388 leukemia cells. P388/ADR was completely cross-resistant to a spectrum of anthracycline derivatives. Cross-resistance was observed to nonanthracycline DNA intercalating agents (with the exception of anthramycin), to agents which interfere with mitotic spindle function and to antineoplastic inhibitors of protein biosynthesis (with the exception of bruceantin). P388/ADR was sensitive to antimetabolites and alkylating agents. Cross-resistance to several agents (ICRF-159 [4,4''-(1-methyl-1,2-ethanediyl)bis-2,6-piperaninedione], a terephthalanilide, taxol, lymphosarcin, bouvardin and a crude extract of Ervatamia hyneana) was also observed; their mechanisms of action are not clearly defined. This observation proved useful in providing a lead for determination of mechanism of action of some of these drugs. The pattern of cross-resistance of a subline of P388 leukemia resistant to daunorubicin, though not studied extensively, appears to be similar to that of P388/ADR.