title: DNA damage in blood leukocytes of individuals with sickle cell disease treated with hydroxyurea.
abstract: Hydroxyurea (HU) plays an important role in the treatment of patients with sickle cell disease (SCD). Although HU has been associated with an increased risk of leukemia in some patients with myeloproliferative disorders, the mutagenic and carcinogenic potential of HU has not been established. This study investigated levels of DNA damage using the alkaline (pH>13) comet assay to analyze peripheral blood leukocytes sampled from 28 patients with SCD treated with HU (SCHU) and from 28 normal individuals. The damage index (DI) in the SCHU group was significantly higher than in controls (p<0.05). Gender, smoking or age were not associated with DNA damage in controls or SCHU individuals. In the group of SCHU individuals, mean HU dose and DI were positively correlated, and individuals who received a mean dose of >20 mg/kg HU (DI=24.9+/-5.5) showed significantly more DNA damage than those who received < or =20 mg/kg HU (DI=14.6+/-1.8) (p<0.05). Individuals treated for > or =42 months (DI=23.1+/-4.2) showed significantly greater DNA damage than those treated for <42 months (13.6+/-1.9) (p<0.05). DI was inversely correlated with body mass index in the SCHU group.
authors.affiliation: Hematology and Bone Marrow Transplant Service, Hospital de Clínicas de Porto Alegre (HCPA), Rua Ramiro Barcelos, CEP 90035-903, Porto Alegre, RS, Brazil.
authors.forename: João Ricardo
authors.initials: JR
authors.lastname: Friedrisch
authors.forename: Daniel
authors.initials: D
authors.lastname: Prá
authors.forename: Sharbel Weidner
authors.initials: SW
authors.lastname: Maluf
authors.forename: Christina Matzembacher
authors.initials: CM
authors.lastname: Bittar
authors.forename: Michelle
authors.initials: M
authors.lastname: Mergener
authors.forename: Tiago
authors.initials: T
authors.lastname: Pollo
authors.forename: Michele
authors.initials: M
authors.lastname: Kayser
authors.forename: Maria Aparecida Lima
authors.initials: MA
authors.lastname: da Silva
authors.forename: João Antonio Pêgas
authors.initials: JA
authors.lastname: Henriques
authors.forename: Lucia Mariano
authors.initials: LM
authors.lastname: da Rocha Silla
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood / Q000188:drug therapy*; D000986:Antisickling Agents / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D020552:Comet Assay; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000009:adverse effects* / Q000627:therapeutic use; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged
chemical_list: D000986:Antisickling Agents; D006918:Hydroxyurea