This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rabes, H. M. Articles by Tuczek, H. V. Search for Related Content PubMed PubMed Citation Articles by Rabes, H. M. Articles by Tuczek, H. V.

Synchronization of Hepatocellular DNA Synthesis in Regenerating Rat Liver by Continuous Infusion of Hydroxyurea¹

Institute of Pathology, University of Munich, 8 Munich 2, Thalkirchner Str. 36, Federal Republic of Germany

Hydroxyurea (HU) inhibited DNA synthesis in the livers of partially hepatectomized rats. After an i.v. infusion of HU begun in the late G₁ phase and continued for periods of up to 30 hr, all hepatocytes scheduled to embark on DNA synthesis in a characteristic intralobular sequence during this time interval accumulated at the G₁-S boundary. The effective dose was 1.25 mmoles/kg/hr, preceded by a single injection of 1.69 mmoles/kg. Serum levels of HU rose slightly during continuous infusion and decreased after termination, with a half-life of about 80 min. Liver weight increased during HU infusion.

The G₁-S blockade was rapidly reversed in the liver after the end of HU infusion. The specific activity of DNA increased to a maximum between 3 and 5 hr. [³H]Thymidine labeling indices reached about 80%. Intralobular distribution of labeled hepatocytes was congruent to the pattern seen in partially hepatectomized rats after a continuous [³H]thymidine infusion of equal duration. The beginning of DNA synthesis in nonparenchymal cells was delayed, as compared with hepatocytes.

Vincristine infusion for 12 hr after release from the HU block arrested about 40% of the hepatocytes in mitosis, indicating that a large fraction of cells progressed through the cycle after the prolonged HU block.

Partially resected rat liver appeared to be rather resistant to the unfavorable consequences of "unbalanced growth" during the protracted inhibition of DNA synthesis, providing a useful model for synchronization of DNA synthesis in a differentiated resting organ triggered into active growth.

¹ Supported by Grants from Deutsche Forschungsgemeinschaft, Bonn-Bad Godesberg, Germany.

² To whom requests for reprints should be addressed.

Received 9/ 9/76. Accepted 12/20/76.

This article has been cited by other articles:

				D. E. Cressman, L. E. Greenbaum, R. A. DeAngelis, G. Ciliberto, E. E. Furth, V. Poli, and R. Taub Liver Failure and Defective Hepatocyte Regeneration in Interleukin-6-Deficient Mice Science, November 22, 1996; 274(5291): 1379 - 1383. [Abstract] [Full Text]