Abstract

HYDROXYUREA: ITS THERAPEUTIC POTENTIAL AND TOXICITY

Md. Fahim Ahmad, Mohd. Owais Ansari, Nuzhat Parveen, Shoeb Ahmad, Sana Jameel and *G. G. H. A. Shadab

Abstract

Hydroxyurea (HU) is an antineoplastic drug. It has widespread usagein the treatment of both malignant and nonmalignant diseases likeSickle-cell anaemia and HIV infections. It acts on the enzymeribonucleotide reductase to inhibit the conversion of ribonucleotidesinto deoxyribonucleotides, thereby limiting DNA biosynthesis. Theprincipal use of HU has been as a myelosuppressive agent in thetreatment of myeloproliferative syndromes, particularly chronicmyelogenous leukemia and polycythemia vera. Although treatment ofchronic myelogenous leukemia with HU for many years has beenreserved for patients whose disease was no long irresponsive tobusulfan. HU acts as a cytotoxic and antineoplastic agent thatspecifically affects the S phase and interrupts the cell cycle in the G2 and S phases. Studiesshowed that HU causes rapid cell death through the initiation of uncontrolled free radicalchain reaction. Free radical reactions are able to devastate cellular metabolism quickly byinactivating enzymes, cross-linking DNA and altering membrane function through lipid autooxidation.Despite being very frequently used in the treatment of several malignant and nonmalignantdiseases, prolonged use of HU has been reported to cause mutation and clastogeniceffects in several in vitro systems, as well as cytogenetic damage in exposed mice. It has alsoshown a wide variety of toxic effects, like induction of chromosomal aberrations andcytotoxicity, as well as a well established genotoxic activity in cell culture and rodent models.

Keywords: Hydroxyurea, antineoplastic drug, ribonucleotide reductase, cytotoxic, genotoxic.