Mitoxantrone treatment of murine myeloid leukaemia sublines

Abstract

The low-cell-dose (LD) and the high-cell-dose (HD) transplant variants of the SA7 murine myeloid leukaemia cell line have different growth characteristics and clinical presentations. In addition, the low-cell-dose transplant subline (SA7LD) was more responsive than the high-cell-dose variant (SA7HD) to mitoxantrone treatment in vivo. Bone-marrow cells of mice cured of SA7LD leukaemia, as well as bone-marrow cells of normal mice treated with priming doses of mitoxantrone in vivo became significantly (p = 0.012) less sensitive to subsequent treatment with mitoxantrone in vitro. This effect was detected by both the colony assay and the tritiated thymidine uptake assay. There appears to be a correlation between the ability of normal bone-marrow cells present in leukaemic mice to develop this protective effect and their ability to survive chemotherapy with mitoxantrone. The protective effect was "lost" by bone-marrow cells of mice dying while in remission. Doses of mitoxantrone that resulted in the loss of protective effect by bone-marrow cells of normal mice were found to be fatal to SA7HD leukaemia-bearing mice. However, these doses were not toxic to normal mice.