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Genes 2016, 7(11), 99; doi:10.3390/genes7110099

The Cell Killing Mechanisms of Hydroxyurea

1
Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, OH 45435, USA
2
Wadsworth Center, NYSDOH, 120 New Scotland Ave., Albany, NY 12208, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Eishi Noguchi
Received: 22 September 2016 / Revised: 3 November 2016 / Accepted: 9 November 2016 / Published: 17 November 2016
(This article belongs to the Special Issue DNA Replication Controls)
View Full-Text   |   Download PDF [1746 KB, uploaded 17 November 2016]   |  

Abstract

Hydroxyurea is a well-established inhibitor of ribonucleotide reductase that has a long history of scientific interest and clinical use for the treatment of neoplastic and non-neoplastic diseases. It is currently the staple drug for the management of sickle cell anemia and chronic myeloproliferative disorders. Due to its reversible inhibitory effect on DNA replication in various organisms, hydroxyurea is also commonly used in laboratories for cell cycle synchronization or generating replication stress. However, incubation with high concentrations or prolonged treatment with low doses of hydroxyurea can result in cell death and the DNA damage generated at arrested replication forks is generally believed to be the direct cause. Recent studies in multiple model organisms have shown that oxidative stress and several other mechanisms may contribute to the majority of the cytotoxic effect of hydroxyurea. This review aims to summarize the progress in our understanding of the cell-killing mechanisms of hydroxyurea, which may provide new insights towards the improvement of chemotherapies that employ this agent. View Full-Text
Keywords: hydroxyurea; ribonucleotide reductase; oxidative stress; cytokinesis arrest; DNA replication checkpoint; cell cycle hydroxyurea; ribonucleotide reductase; oxidative stress; cytokinesis arrest; DNA replication checkpoint; cell cycle
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Singh, A.; Xu, Y.-J. The Cell Killing Mechanisms of Hydroxyurea. Genes 2016, 7, 99.

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