Radical mechanism of hydroxyurea side toxicity

• 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
• EISSN: 1732-2693

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.