Source:http://linkedlifedata.com/resource/pubmed/id/21542824
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2011-6-9
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pubmed:abstractText |
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.
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pubmed:grant |
http://linkedlifedata.com/resource/pubmed/grant/2 P30 CA021765,
http://linkedlifedata.com/resource/pubmed/grant/R01-HL-090941,
http://linkedlifedata.com/resource/pubmed/grant/T32 CA070089-11,
http://linkedlifedata.com/resource/pubmed/grant/T32-CA070089,
http://linkedlifedata.com/resource/pubmed/grant/U54-HL070590-07
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1365-2141
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pubmed:author | |
pubmed:copyrightInfo |
© 2011 Blackwell Publishing Ltd.
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pubmed:issnType |
Electronic
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pubmed:volume |
154
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
134-40
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pubmed:meshHeading |
pubmed-meshheading:21542824-Adolescent,
pubmed-meshheading:21542824-Adult,
pubmed-meshheading:21542824-Anemia, Sickle Cell,
pubmed-meshheading:21542824-Antisickling Agents,
pubmed-meshheading:21542824-Cells, Cultured,
pubmed-meshheading:21542824-Child,
pubmed-meshheading:21542824-Child, Preschool,
pubmed-meshheading:21542824-Chromosome Aberrations,
pubmed-meshheading:21542824-Cross-Sectional Studies,
pubmed-meshheading:21542824-DNA Damage,
pubmed-meshheading:21542824-DNA Repair,
pubmed-meshheading:21542824-Drug Administration Schedule,
pubmed-meshheading:21542824-Humans,
pubmed-meshheading:21542824-Hydroxyurea,
pubmed-meshheading:21542824-Middle Aged
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pubmed:year |
2011
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pubmed:articleTitle |
Chromosome damage and repair in children with sickle cell anaemia and long-term hydroxycarbamide exposure.
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pubmed:affiliation |
Department of Hematology, St Jude Children's Research Hospital, Memphis, TN 38105, USA. patrick.mcgann@stjude.org
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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