Comparison of the cytotoxicity of amsacrine and its analogue CI-921 against cultured human and mouse bone marrow tumour cells

Abstract

Human and mouse bone marrow cells were cultured for 1 h in the presence of either the antileukaemia drug amsacrine or its 4-methyl, 5-[ N-methyl]carboxamide disubstituted analogue CI- 921, before being plated in methylcellulose medium to determine the survival of granulocytemacrophage colony forming units (CFU-GM). The drug concentration required for 50% reduction in survival was approx. 0.4 μM for both drugs and was similar for both human and mouse cells. A comparison of the two drugs was then made, at an added drug concentration of 0.5 μM, using cultured mouse L 1210 and P 388 leukaemia, Lewis lung carcinoma cell lines LLAK and LLTC, human Jurkat leukaemia, human histiocytic lymphoma U 937 and human colon carcinoma SW 620. The sensitivity of the mouse lines for amsacrine was in the order L 1210 > P 388 > LLAK > LLTC, similar to the in vivo sensitivity. The selectivity of CI- 921 for L 1210 versus bone marrow, and for LLAK versus L 1210 or P 388, was greater than that of amsacrine, again in keeping with its in vivo properties. The sensitivity of the human Jurkat and U 937 lines for amsacrine was intermediate between that of L 1210 and P 388, while SW 620 was resistant. The selectivity of CI- 921 for Jurkat and U 937 versus bone marrow was greater than that of amsacrine, suggesting that CI- 921 could have additional advantages over amsacrine in the treatment of some tumours.