Selective killing of murine leukemic cells by adenosine triphosphate (ATP): a study of the value of autologous bone marrow transplantation.
To assess the value of adenosine triphosphate (ATP) for ex vivo purging of leukemic cells in autologous bone marrow transplantation, its biological effects on the murine leukemic cell lines (WEHI3B and L1210) and normal murine bone marrow hemopoietic stem cells (CFU-C and CFU-S) were studied. After treatment with 4 mM of ATP for 6 h, the number of viable WEHI3B cells decreased to less than 0.1% of that of the control. Furthermore, 3H-thymidine incorporations were also completely inhibited in both WEHI3B cells and L1210 cells. These phenomena were related to the concentration and exposure period of ATP. Treatment of bone marrow mononuclear cells with ATP under the same condition reduced the number of CFU-C, day 9 CFU-S and day 12 CFU-S to only 58.5 +/- 8.7%, 92.6 +/- 8.2% and 83.5 +/- 28.5%, respectively, with no change in the number of marrow nucleated cells. Although the effect of ATP is not entirely specific to leukemic cells, these findings provide evidence that ATP is useful for purging residual tumor cells in autologous bone marrow transplantation.
First Department of Internal Medicine, Nihon University School of Medicine, Tokyo.
Y
Y
Hatta
S
S
Aizawa
A
A
Horikoshi
M
M
Baba
T
T
Horie
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D016465:Bone Marrow Purging / Q000379:methods*; D016026:Bone Marrow Transplantation; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D007939:Leukemia L1210 / Q000201:enzymology / Q000601:surgery; D007942:Leukemia, Experimental / Q000201:enzymology / Q000601:surgery*; D008297:Male; D051379:Mice; D014182:Transplantation, Autologous
D000255:Adenosine Triphosphate; D017301:Ca(2+) Mg(2+)-ATPase