Comparison of the cytotoxicity of amsacrine and its analogue CI-921 against cultured human and mouse bone marrow tumour cells.
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 granulocyte-macrophage colony forming units (CFU-GM). The drug concentration required for 50% reduction in survival was approx. 0.4 microM 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 microM, using cultured mouse L1210 and P388 leukaemia, Lewis lung carcinoma cell lines LLAK and LLTC, human Jurkat leukaemia, human histiocytic lymphoma U937 and human colon carcinoma SW620. The sensitivity of the mouse lines for amsacrine was in the order L1210 greater than P388 greater than LLAK greater than LLTC, similar to the in vivo sensitivity. The selectivity of CI-921 for L1210 versus bone marrow, and for LLAK versus L1210 or P388, was greater than that of amsacrine, again in keeping with its in vivo properties. The sensitivity of the human Jurkat and U937 lines for amsacrine was intermediate between that of L1210 and P388, while SW620 was resistant. The selectivity of CI-921 for Jurkat and U937 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.
Ching
L M
LM
Cancer Research Laboratory, University of Auckland Medical School, New Zealand.
Finlay
G J
GJ
Joseph
W R
WR
Baguley
B C
BC
D000677:Amsacrine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy; D007942:Leukemia, Experimental / Q000188:drug therapy*; D051379:Mice; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D000677:Amsacrine; C042315:asulacrine