Kinetics and cell killing in dividing and nondividing leukemic cells in vitro and in vivo by natural splenic cytotoxic factor.
Ultrafiltered splenic extracts (30,000-50,000 daltons) were specifically cytotoxic in crowded cultures of murine leukemic lymphoblasts but were only inhibitory toward normal lymphocytes or sparse cultures of leukemic cells. This expression of cytotoxicity was quantitated by (i) vital dye exclusion, (ii) cytochemical metods, and (iii) the increased survival time of mice injected with L-1210 leukemic cells incubated in vitro with splenic extract. Selective cytotoxicity of splenic extract was not due to medium depletion or to complement-mediated cytolysis and could not be replicated using similar extracts of other lymphoid and nonlymphoid tissues. The selective effect of splenic extract on leukemic cells was characterized by the progressive shedding of cytochemically demonstrable RNA and the corresponding inhibition of 3H-uridine and 3H-thymidine incorporation. The comparison of progressive and gradual expression of cytotoxicity by splenic extract with the S phase specific inhibitor cytosine arabinoside suggests that the former is cytotoxic against leukemic cells predominantly in the G1 phase of the cell cycle.
D000818:Animals; D002417:Cattle; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D007700:Kinetics; D007939:Leukemia L1210 / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology*; D013552:Swine; D014020:Tissue Extracts / Q000494:pharmacology*
D014020:Tissue Extracts