Two Assays to Evaluate Potential Genotoxic Effects of Hydroxyurea in Sickle Cell Disease Patients

Abstract

Hydroxycarbamide, well known in clinical settings as hydroxyurea (HU), is an antineoplastic agent inhibiting the ribonucleotide reductase enzyme, and thus, the conversion of ribonucleotides into deoxyribonucleotides. A concern about long term side effects of HU treatment in sickle cell disease patients, particularly genotoxicity, has often been evoked. The present study assessed two suitable methods to evaluate oxidative DNA damage associated with HU: the comet assay on blood lymphocytes and the quantification of urinary excretion of 8-oxodeoxyguanosine (8-oxodG). Both methods were applied in a preliminary study including seven sickle cell disease patients treated with HU, seven untreated sickle cell disease patients and five healthy volunteers. Concerning DNA damage, the comet assay and the 8-oxodG assay did not reveal any significant differences among the three groups. Methodologies used in this pilot study could be suitable to carry out further research in this area including a larger size sample setting.

Hydroxyurea (hydroxycarbamide) genotoxicity in pediatric patients with sickle cell disease

“…was performed with some modifications . This method was first applied by the authors to estimate HU genotoxicity in a small population of patients with SCD in the scope of a pilot study …”

“…19 This method was first applied by the authors to estimate HU genotoxicity in a small population of patients with SCD in the scope of a pilot study. 20 Microscope slides were precoated by dipping them in a 1% solution The comet parameter considered in this study was tail DNA, a parameter linear with damage intensity. Statistical analysis was done as recommended.…”