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Growth Inhibition by Thymidine of Leukemic HL-60 and Normal Human Myeloid Progenitor Cells¹

Laboratory of Clinical Biochemistry, Baltimore Cancer Research Program, Division of Cancer Treatment, National Cancer Institute, Baltimore, Maryland 21201

We compared the relative susceptibility of HL-60, a human acute progranulocytic leukemia cell line, and the normal human myeloid progenitor cell, the colony-forming unit in culture, to growth inhibition by thymidine. Normal human myeloid colony formation was more sensitive to thymidine than was HL-60 colony formation, the former being inhibited by 0.5 mM thymidine and the latter by 5.0 mM. Colony inhibition by thymidine was irreversible in both cases after a seven-day incubation of the colony-forming unit in culture in liquid medium enriched with thymidine and subsequent replating in thymidine-free soft agar. Thymidine-induced inhibition of HL-60 cloning could be partially prevented by deoxycytidine, whereas normal myeloid cloning could not, suggesting that high-concentration thymidine may affect processes necessary for cloning in addition to deoxyribonucleotide synthesis. HL-60 growth in liquid suspension culture could be suppressed transiently by 1.0 mM thymidine, suppressed totally by 5.0 mM thymidine, and rescued completely by concomitant addition of deoxycytidine. The development of resistance to 1.0 mM thymidine could not be accounted for by reduction in thymidine pool size or by reduction in thymidine kinase activity. Replating of HL-60 cells growing in the presence of 1.0 mM thymidine in liquid medium in thymidine-free soft agar produced significant colony inhibition, also suggesting that thymidine affects more than just deoxyribonucleotide synthesis or that the clonogenic HL-60 cell represents a distinct subpopulation with more sensitive deoxyribonucleotide-synthetic control mechanisms.

¹ Presented in part at the Eighth Annual Meeting of the International Society for Experimental Hematology, August 21 to 24, 1979, Rotterdam, The Netherlands.

² To whom requests for reprints should be addressed.

Received 6/24/80. Accepted 2/18/81.