Document Detail


Necrosis is increased in lymphoblastoid cell lines from children with autism compared with their non-autistic siblings under conditions of oxidative and nitrosative stress.
MedLine Citation:
PMID:  23766106     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Autism spectrum disorders are a heterogeneous group of neurodevelopmental conditions characterised by impairments in reciprocal social interaction, communication and stereotyped behaviours. As increased DNA damage events have been observed in a range of other neurological disorders, it was hypothesised that they would be elevated in lymphoblastoid cell lines (LCLs) obtained from children with autism compared with their non-autistic siblings. Six case-sibling pairs of LCLs from children with autistic disorder and their non-autistic siblings were obtained from the Autism Genetic Resource Exchange (AGRE) and cultured in standard RPMI-1640 tissue culture medium. Cells were exposed to medium containing either 0, 25, 50, 100 and 200 µM hydrogen peroxide (an oxidative stressor) or 0, 5, 10, 20 and 40 µM s-nitroprusside (a nitric oxide producer) for 1h. Following exposure, the cells were microscopically scored for DNA damage, cytostasis and cytotoxicity biomarkers as measured using the cytokinesis-block micronucleus cytome assay. Necrosis was significantly increased in cases relative to controls when exposed to oxidative and nitrosative stress (P = 0.001 and 0.01, respectively). Nuclear division index was significantly lower in LCLs from children with autistic disorder than their non-autistic siblings when exposed to hydrogen peroxide (P = 0.016), but there was no difference in apoptosis, micronucleus frequency, nucleoplasmic bridges or nuclear buds. Exposure to s-nitroprusside significantly increased the number of micronuclei in non-autistic siblings compared with cases (P = 0.003); however, other DNA damage biomarkers, apoptosis and nuclear division did not differ significantly between groups. The findings of this study show (i) that LCLs from children with autism are more sensitive to necrosis under conditions of oxidative and nitrosative stress than their non-autistic siblings and (ii) refutes the hypothesis that children with autistic disorder are abnormally susceptible to DNA damage.
Authors:
Penelope A E Main; Philip Thomas; Adrian Esterman; Michael F Fenech
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Mutagenesis     Volume:  28     ISSN:  1464-3804     ISO Abbreviation:  Mutagenesis     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-06-14     Completed Date:  2014-01-16     Revised Date:  2014-07-01    
Medline Journal Info:
Nlm Unique ID:  8707812     Medline TA:  Mutagenesis     Country:  England    
Other Details:
Languages:  eng     Pagination:  475-84     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects,  genetics
Autistic Disorder / genetics*,  metabolism*
Cell Line
Child
Child Development Disorders, Pervasive / genetics,  metabolism
Child, Preschool
DNA Damage / drug effects,  genetics
Humans
Hydrogen Peroxide / pharmacology
Lymphocytes / metabolism
Male
Necrosis / genetics*,  metabolism*
Nitroprusside / pharmacology
Nitrosation
Oxidation-Reduction
Siblings
Stress, Physiological*
Grant Support
ID/Acronym/Agency:
1U24MH081810/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
169D1260KM/Nitroprusside; BBX060AN9V/Hydrogen Peroxide
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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