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Dörmér, P.G. ; Böhmer, R.M.

Cell-cycle-dependent and -independent damage to rat haemopoiesis by hydroxyurea.

Cell Prolif. 17, 619-628 (1984)
DOI
Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.
The generally accepted cell-killing effect of hydroxyurea (HU) on S-phase cells, as well as its potential to arrest cells at the G1/S boundary, hardly explain its benefit for application in human chronic myelogenous leukaemia. Studies were therefore performed in rat haemopoiesis in order to quantify the cell-killing effect on various phases of the cell cycle. For this purpose, the [3H]thymidine ([3H]TdR) labelling index and the specific activity of [3H]TdR in the DNA-synthesizing fraction of cells were determined after a non-cytoreductive dose of 25 mg/kg HU, as well as a medium cytoreductive dose of 100 mg/kg. Furthermore, flow cytometric DNA histograms and absolute as well as differential cell counts of femoral bone marrow were performed after 100 mg/kg HU. The results indicate a predominant cell kill in G1 encompassing almost all 2c cells in the proliferative pool, while the S-phase fraction is not even reduced to half its initial value. The specific activity of [3H]TdR in cell synthesizing DNA, as well as the labelling index after HU show an initial dip and a tendency to recovery, as has been observed in many other cell systems. Instead of a complete restoration, however, there is a second depression of these parameters lasting for at least one cell cycle. The results are interpreted as a partly cell-cycle-dependent and partly independent action of HU in this cell system. The independent component may be attributed to the repeatedly described direct interference of HU with DNA. In rat haemopoiesis, therefore, this direct effect of HU on the DNA strands appears to be much more pronounced than in cell-culture systems and other mammalian tissues. In view of these findings, some caution should be taken in using HU for the determination of the S-phase fraction by way of a suicide experiment.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 0008-8730
e-ISSN 1365-2184
Journal Cell Proliferation
Quellenangaben Volume: 17, Issue: 6, Pages: 619-628 Article Number: , Supplement: ,
Publisher Blackwell
Publishing Place Oxford [u.a.] ; Berlin ; Vienna
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institut für Experimentelle Hämatologie