An in vivo study on the synchronizing effect of hydroxyurea.
The effect of hydroxyurea (HU; 0.5 mg/g body wt) on L 1210 ascites tumor cells has been studied using various cell kinetic methods. In contrast to the general assumption that HU blocks cells at the G1/S boundary [J. Brachet (1985) Molecular Cytology, Vol. I, p. 266, Academic Press, New York], the present results show that the cells are not held at G1/S but enter S at about the normal rate and are accumulated in early S phase due to a dose-dependent inhibiting effect of HU on DNA synthesis. Partial synchronization of the cells demonstrated by a distinct mitotic peak 10 h after HU application is not due to a G1/S block of the cells and their subsequent synchronous passage through the cycle after release from the block but is due to rather complex mechanisms of action of HU: a differential cytocidal effect and an effect on the passage of the cells through the cycle, both depending on the position of the cells throughout the cycle. HU kills S-phase cells, mainly cells in early S phase; i.e., a great portion of the cells "accumulated" in early S phase is killed by the drug, while G1-phase cells are almost not affected by the lethal effect of HU. These G1-phase cells pass through the cycle more rapidly after cessation of the HU effect. The same is true for the surviving cells accumulated in early S phase, while part of the cells in the remaining S phase are delayed in their passage through the cycle. This causes partial synchronization, since a great portion of all cells that survive HU treatment reach mitosis at the same time.
Maurer-Schultze
B
B
Institut für Medizinische Strahlenkunde, University of Würzburg, Federal Republic of Germany.
Siebert
M
M
Bassukas
I D
ID
D000818:Animals; D001345:Autoradiography; D002250:Carbon Radioisotopes; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects*; D005260:Female; D006918:Hydroxyurea / Q000494:pharmacology*; D007700:Kinetics; D007939:Leukemia L1210 / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D002250:Carbon Radioisotopes; D014316:Tritium; D013936:Thymidine; D006918:Hydroxyurea