Radical mechanism of hydroxyurea side toxicity

It has been shown that hydroxyurea (HU) induces free radicals which exert cytotoxic effects on cells. However, the molecular mechanism of this effect is still obscure. A possible mechanism for HU-mediated cell death induced by unbalanced growth could be the overproduction, altered accumulation, and...

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Bibliographic Details
Published in:	Postȩpy higieny i medycyny doświadczalnej Vol. 60; p. 516
Main Authors:	Przybyszewski, Waldemar M, Kasperczyk, Janusz
Format:	Journal Article
Language:	Polish
Published:	Poland 2006
Subjects:	Antineoplastic Agents - therapeutic use Antineoplastic Agents - toxicity Antioxidants - therapeutic use Cell Death Cell Division DNA, Neoplasm - drug effects Dose-Response Relationship, Drug Erythrocytes - drug effects Free Radical Scavengers - therapeutic use Hydroxyurea - therapeutic use Hydroxyurea - toxicity Osmotic Fragility - drug effects
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Summary:	It has been shown that hydroxyurea (HU) induces free radicals which exert cytotoxic effects on cells. However, the molecular mechanism of this effect is still obscure. A possible mechanism for HU-mediated cell death induced by unbalanced growth could be the overproduction, altered accumulation, and progressive leakage of many hydrolytic enzymes through the cell membrane, leading to "lytic" cell death. Protection by antioxidants and radicals scavengers does not change the inhibition of DNA synthesis dependent on ribonucleotide reductase, the main mechanism of the antineoplastic activity of HU. These observations support the hypothesis that membranes are targets for the side effects of HU toxicity. Damage of erythrocytes and granulocytes seems to be an important clinical feature of the HU side toxicity generating free radicals.
ISSN:	1732-2693