S-Phase Cells of Rapidly Growing and Resting Populations

The effects of methotrexate on L5178Y cells from logarithmically growing cultures and from resting cultures were studied. Methotrexate killed cells 6.7 times faster and produced 20-fold greater inhibition of deoxyuridine incorporation into DNA in the cells from logarithmic as compared to resting cultures. The antifolate also acutely suppressed the incorporation of thymidine into DNA by cells from logarithmic cultures but had no effect on that by cells from resting cultures. These differences in the effects of methotrexate on the S-phase cells from cultures of different growth rates are interpreted in the light of current hypotheses relating cell kinetics to the cytocidal effects of antimetabolites.