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Molecular Pharmacology, Vol 5, 557-564, Copyright © 1969 by the American Society for Pharmacology and Experimental Therapeutics

S-Phase Cells of Rapidly Growing and Resting Populations

Differences in Response to Methotrexate

WILLIAM M. HRYNIUK 1, GLENN A. FISCHER 1, and JOSEPH R. BERTINO 1

1 Departments of Pharmacology and Medicine, Yale University School of Medicine, New Haven, Connecticut 06510

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.

Note:
ACKNOWLEDGMENTS We thank Mrs. Inger-Anne Skjeltorp for her meticulous technical assistance, and Dr. G. J. Goldenberg for his constructive criticism of this manuscript.

Submitted on July 23, 1969




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