title: Length of treatment and dose as determinants of mutagenicity in sickle cell disease patients treated with hydroxyurea.
abstract: Hydroxyurea (HU) is an antineoplastic drug widely used in the clinical management of patients with sickle cell disease (SCD), and many questions related with its use remain unresolved. Given the severity of SCD, HU benefits, although not thoroughly confirmed, seem to outweigh its potential carcinogenicity. This study aimed to assess the genotoxicity associated with HU dose and treatment length by evaluating mutagenicity in patients with SCD treated with HU (SCHU) using the cytokinesis-block micronucleus assay (CBMN) in white cells. The study was conducted with 35 individuals in the SCHU group and 34 controls matched according to age, sex and smoking habit. CBMN results showed an increase (p=0.032) in the number of micronuclei (MN), but not of nucleoplasmic bridges (NPB) or nuclear buds (NBUD) in the SCHU group. The increased frequency of MN in the SCHU group was significantly correlated with treatment length and final HU dose, which confirms that patients with SCD treated with HU should be carefully monitored to reduce the risk of carcinogenicity.
authors.affiliation: Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA), Rua Ramiro Barcelos 2350, CEP 90035-003, Porto Alegre, RS, Brazil.
authors.forename: Sharbel
authors.initials: S
authors.lastname: Maluf
authors.forename: Daniel
authors.initials: D
authors.lastname: Prá
authors.forename: João R
authors.initials: JR
authors.lastname: Friedrisch
authors.forename: Christina
authors.initials: C
authors.lastname: Bittar
authors.forename: Maria A Lima
authors.initials: MA
authors.lastname: da Silva
authors.forename: João A
authors.initials: JA
authors.lastname: Henriques
authors.forename: Lucia
authors.initials: L
authors.lastname: Silla