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Chromosome damage and repair in children with sickle cell anaemia and long-term hydroxycarbamide exposure.


ABSTRACT: Hydroxycarbamide (hydroxyurea) provides laboratory and clinical benefits for adults and children with sickle cell anaemia (SCA). Given its mechanism of action and prior reports of genotoxicity, concern exists regarding long-term toxicities and possible carcinogenicity. We performed cross-sectional analyses of chromosome stability using peripheral blood mononuclear cells (PBMC) from 51 children with SCA and 3-12 years of hydroxycarbamide exposure (mean age 13·2 ± 4·1 years), compared to 28 children before treatment (9·4 ± 4·7 years). Chromosome damage was less for children receiving hydroxycarbamide than untreated patients (0·8 ± 1·2 vs. 1·9 ± 1·5 breaks per 100 cells, P = 0·004). There were no differences in repairing chromosome breaks after in vitro radiation; PBMC from children taking hydroxycarbamide had equivalent 2 Gy-induced chromosome breaks compared to untreated patients (30·8 ± 16·1 vs. 31·7 ± 8·9 per 100 cells, P = not significant). Radiation plus hydroxycarbamide resulted in similar numbers of unrepaired breaks in cells from children on hydroxycarbamide compared to untreated patients (95·8 ± 44·2 vs. 76·1 ± 23·1 per 100 cells, P = 0·08), but no differences were noted with longer exposure (97·9 ± 42·8 breaks per 100 cells for 3-6 years of hydroxycarbamide exposure vs. 91·2 ± 48·4 for 9-12 years of exposure). These observations provide important safety data regarding long-term risks of hydroxycarbamide exposure for children with SCA, and suggest low in vivo mutagenicity and carcinogenicity.

SUBMITTER: McGann PT 

PROVIDER: S-EPMC3111895 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Chromosome damage and repair in children with sickle cell anaemia and long-term hydroxycarbamide exposure.

McGann Patrick T PT   Howard Thad A TA   Flanagan Jonathan M JM   Lahti Jill M JM   Ware Russell E RE  

British journal of haematology 20110504 1


Hydroxycarbamide (hydroxyurea) provides laboratory and clinical benefits for adults and children with sickle cell anaemia (SCA). Given its mechanism of action and prior reports of genotoxicity, concern exists regarding long-term toxicities and possible carcinogenicity. We performed cross-sectional analyses of chromosome stability using peripheral blood mononuclear cells (PBMC) from 51 children with SCA and 3-12 years of hydroxycarbamide exposure (mean age 13·2 ± 4·1 years), compared to 28 childr  ...[more]

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