Mitochondrial mutagenesis induced by tumor-specific radiation bystander effects.

Hdl Handle:
http://hdl.handle.net/10147/207514
Title:
Mitochondrial mutagenesis induced by tumor-specific radiation bystander effects.
Authors:
Gorman, Sheeona; Fox, Edward; O'Donoghue, Diarmuid; Sheahan, Kieran; Hyland, John; Mulcahy, Hugh; Loeb, Lawrence A; O'Sullivan, Jacintha
Affiliation:
Centre for Colorectal Disease, St. Vincent's University Hospital, Elm Park,, Dublin 4, Ireland.
Citation:
J Mol Med (Berl). 2010 Jul;88(7):701-8. Epub 2010 Mar 28.
Journal:
Journal of molecular medicine (Berlin, Germany)
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207514
DOI:
10.1007/s00109-010-0616-3
PubMed ID:
20349220
Abstract:
The radiation bystander effect is a cellular process whereby cells not directly exposed to radiation display cellular alterations similar to directly irradiated cells. Cellular targets including mitochondria have been postulated to play a significant role in this process. In this study, we utilized the Random Mutation Capture assay to quantify the levels of random mutations and deletions in the mitochondrial genome of bystander cells. A significant increase in the frequency of random mitochondrial mutations was found at 24 h in bystander cells exposed to conditioned media from irradiated tumor explants (p = 0.018). CG:TA mutations were the most abundant lesion induced. A transient increase in the frequency of random mitochondrial deletions was also detected in bystander cells exposed to conditioned media from tumor but not normal tissue at 24 h (p = 0.028). The increase in both point mutations and deletions was transient and not detected at 72 h. To further investigate mitochondrial dysfunction, mitochondrial membrane potential and reactive oxygen species were assessed in these bystander cells. There was a significant reduction in mitochondrial membrane potential and this was positively associated with the frequency of random point mutation and deletions in bystander cells treated with conditioned media from tumor tissue (r = 0.71, p = 0.02). This study has shown that mitochondrial genome alterations are an acute consequence of the radiation bystander effect secondary to mitochondrial dysfunction and suggests that this cannot be solely attributable to changes in ROS levels alone.
Language:
eng
MeSH:
Aged; *Bystander Effect; Culture Media, Conditioned/metabolism; DNA, Mitochondrial/*radiation effects; Female; Gamma Rays; Humans; Male; Membrane Potential, Mitochondrial/radiation effects; Mitochondria/*genetics/metabolism/*radiation effects; *Mutation; Neoplasms/*metabolism; Point Mutation; Reactive Oxygen Species/metabolism; Sequence Deletion
ISSN:
1432-1440 (Electronic); 0946-2716 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorGorman, Sheeonaen_GB
dc.contributor.authorFox, Edwarden_GB
dc.contributor.authorO'Donoghue, Diarmuiden_GB
dc.contributor.authorSheahan, Kieranen_GB
dc.contributor.authorHyland, Johnen_GB
dc.contributor.authorMulcahy, Hughen_GB
dc.contributor.authorLoeb, Lawrence Aen_GB
dc.contributor.authorO'Sullivan, Jacinthaen_GB
dc.date.accessioned2012-02-01T10:29:59Z-
dc.date.available2012-02-01T10:29:59Z-
dc.date.issued2012-02-01T10:29:59Z-
dc.identifier.citationJ Mol Med (Berl). 2010 Jul;88(7):701-8. Epub 2010 Mar 28.en_GB
dc.identifier.issn1432-1440 (Electronic)en_GB
dc.identifier.issn0946-2716 (Linking)en_GB
dc.identifier.pmid20349220en_GB
dc.identifier.doi10.1007/s00109-010-0616-3en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207514-
dc.description.abstractThe radiation bystander effect is a cellular process whereby cells not directly exposed to radiation display cellular alterations similar to directly irradiated cells. Cellular targets including mitochondria have been postulated to play a significant role in this process. In this study, we utilized the Random Mutation Capture assay to quantify the levels of random mutations and deletions in the mitochondrial genome of bystander cells. A significant increase in the frequency of random mitochondrial mutations was found at 24 h in bystander cells exposed to conditioned media from irradiated tumor explants (p = 0.018). CG:TA mutations were the most abundant lesion induced. A transient increase in the frequency of random mitochondrial deletions was also detected in bystander cells exposed to conditioned media from tumor but not normal tissue at 24 h (p = 0.028). The increase in both point mutations and deletions was transient and not detected at 72 h. To further investigate mitochondrial dysfunction, mitochondrial membrane potential and reactive oxygen species were assessed in these bystander cells. There was a significant reduction in mitochondrial membrane potential and this was positively associated with the frequency of random point mutation and deletions in bystander cells treated with conditioned media from tumor tissue (r = 0.71, p = 0.02). This study has shown that mitochondrial genome alterations are an acute consequence of the radiation bystander effect secondary to mitochondrial dysfunction and suggests that this cannot be solely attributable to changes in ROS levels alone.en_GB
dc.language.isoengen_GB
dc.subject.meshAgeden_GB
dc.subject.mesh*Bystander Effecten_GB
dc.subject.meshCulture Media, Conditioned/metabolismen_GB
dc.subject.meshDNA, Mitochondrial/*radiation effectsen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshGamma Raysen_GB
dc.subject.meshHumansen_GB
dc.subject.meshMaleen_GB
dc.subject.meshMembrane Potential, Mitochondrial/radiation effectsen_GB
dc.subject.meshMitochondria/*genetics/metabolism/*radiation effectsen_GB
dc.subject.mesh*Mutationen_GB
dc.subject.meshNeoplasms/*metabolismen_GB
dc.subject.meshPoint Mutationen_GB
dc.subject.meshReactive Oxygen Species/metabolismen_GB
dc.subject.meshSequence Deletionen_GB
dc.titleMitochondrial mutagenesis induced by tumor-specific radiation bystander effects.en_GB
dc.contributor.departmentCentre for Colorectal Disease, St. Vincent's University Hospital, Elm Park,, Dublin 4, Ireland.en_GB
dc.identifier.journalJournal of molecular medicine (Berlin, Germany)en_GB
dc.description.provinceLeinster-

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