Differential Lethal Effect of Cytotoxic Agents on Proliferating and Nonproliferating Lymphoid Cells

Dose-survival curves were constructed for the effect of eight cytotoxic agents on both nonproliferating and proliferating bone marrow-derived lymphocytes (B cells). The system used was the primary response of AKR mice to sheep red blood cells. Cytotoxic agents were given either 24 hr before or 24 hr after the antigen stimulation. These times were chosen to represent a time when the majority of B cells that would respond to sheep red blood cells were in a resting and a proliferating state, respectively. B cells were assayed for their ability to yield hemolytic plaque in vitro on Day 4. The degree of differential sensitivity and the shape of dose-survival curves for B cells in different proliferative states to these agents were, in general, compatible with the known cellular effect of these agents in other in vivo cell systems. The smallest difference in sensitivity was noted with 7-radiation and nitrogen mustard. Cytosine arabinoside, amethopterin, vincristine, and 5-fluorouracil had little or no effect on the survival of nonproliferating B cells whereas proliferating B cells were sensitive to these drugs. While nonproliferating B cells were sensitive to both cyclophosphamide and actinomycin D, proliferating B cells were far more susceptible to the cytocidal action of these two agents.