Drug-concentration dependent sensitivity to lysis by antibody and complement, of adriamycin- or mitomycin-treated murine lymphoma cells.
Murine lymphoma cells (RDM4) were pretreated in culture, with Adriamycin (ADM) and with Mitomycin C (Mit C), at different concentrations, for 20 h and carefully washed. In a first series of experiments, they were labelled with 51Cr and used as target to the lytic action of alloantiserum and complement (Ab + c), as appraised by the specific 51Cr release test. It was found that exposures of the prospective target cells to high drug concentrations (e.g. 32 micrograms/ml of ADM or 20 micrograms/ml of Mit C) enhanced their susceptibility to Ab + c killing, whereas exposures to low concentrations (i.e. 0.1 microgram/ml of ADM, or 1 microgram/ml of Mit C) protected them from Ab + c mediated lysis. In a second experimental series, similarly treated RDM4 were pulsed with 3H-TdR after their exposure to Ab + c. In this case, the cytotoxic effect was appraised as "inhibition" of isotope incorporation. Using this second criterion, the protective action of pretreatment with low drug concentrations was confirmed, and was particularly clearcut in the case of ADM. The protective effect of pretreatment with low concentration of ADM (0.1 microgram) was also confirmed in vivo, with the "Winn assay".
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects*; D002460:Cell Line; D003165:Complement System Proteins / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage*; D007167:Immunotherapy; D008223:Lymphoma / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D051379:Mice; D016685:Mitomycin; D008937:Mitomycins / Q000008:administration & dosage*
D008937:Mitomycins; D016685:Mitomycin; D004317:Doxorubicin; D003165:Complement System Proteins