DNA damage in blood leukocytes of individuals with sickle cell disease treated with hydroxyurea.
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.
Friedrisch
João Ricardo
JR
Hematology and Bone Marrow Transplant Service, Hospital de Clínicas de Porto Alegre (HCPA), Rua Ramiro Barcelos, CEP 90035-903, Porto Alegre, RS, Brazil.
Prá
Daniel
D
Maluf
Sharbel Weidner
SW
Bittar
Christina Matzembacher
CM
Mergener
Michelle
M
Pollo
Tiago
T
Kayser
Michele
M
da Silva
Maria Aparecida Lima
MA
Henriques
João Antonio Pêgas
JA
da Rocha Silla
Lucia Mariano
LM
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
D000986:Antisickling Agents; D006918:Hydroxyurea