In vivo characterization of P388 leukemia resistant to mitomycin C.

A line of P388 leukemia resistant to mitomycin C (MMC) was successfully developed in vivo by treating mice bearing parental P388 (P388/0) with MMC followed by serial passage of the surviving leukemic cells. From this P388/MMC line, a subline was derived by not treating the passage mice with MMC (P388/MMC-NP); resistance to MMC was stable for as many as 56 weeks of transplantation. The chemosensitivities of each P388 line to assorted anticancer drugs were compared in vivo. Both P388/MMC and P388/MMC-NP had similar patterns of drug cross-resistance and collateral sensitivity. With respect to alkylating agents (e.g. cyclophosphamide, Platinol and chlorambucil), there was generally a partial degree of cross-resistance, sometimes only detectable at suboptimal dose levels. With respect to DNA binders or intercalators (e.g. actinomycin D, luzopeptin A, amsacrine, doxorubicin), the extent of cross-resistance varied from none (dihydoxyanthraquinone) to marked (doxorubicin). Antimitotic inhibitors (vinblastine and vincristine) were completely cross-resistant, as were some miscellaneous natural agents (rebeccamycin, VP-16, sesbanimide, and elsamicin, a chartreusin analog). Antimetabolites (e.g. methotrexate and 6-thioguanine) showed no cross-resistance and even demonstrated some occasional evidence of collateral effectiveness.