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Array comparative genomic hybridisation analysis of gamma-irradiated human thyrocytes
Stephen P Finn1, Paul Smyth, Esther O'regan
1Department of Histopathology Research, University of Dublin, Trinity College, Room 35/72, Institute of Molecular Medicine, Trinity Centre for Health Sciences, St. James's Hospital , James's Street, Dublin 8, Ireland. sfinn@gofree.indigo.ie
Virchows Archiv : an International Journal of Pathology
|July 20, 2004
Summary
Gamma radiation can induce specific ret rearrangements in human thyroid cells, leading to papillary thyroid carcinoma (PTC). This study observed subtelomeric deletions, suggesting chromosome 10 is a hotspot for radiation damage.
Area of Science:
- Oncology
- Radiation Biology
- Molecular Genetics
Background:
- Thyroid epithelium is susceptible to radiation-induced cancer.
- Thyroid carcinogenesis involves specific ret/papillary thyroid carcinoma (PTC) rearrangements and the papillary phenotype.
- Previous research showed X-rays can induce ret rearrangements in vitro.
Purpose of the Study:
- To determine if gamma radiation from a Caesium 137 source can induce specific ret rearrangements in human thyroid epithelial cells.
- To investigate if DNA copy gain/loss events occur non-randomly following irradiation, consistent with non-random rearrangement events in radiation-induced thyroid carcinogenesis.
Main Methods:
- Irradiation of SV40-immortalised human thyroid epithelial cells with incremental gamma radiation doses.
- Detection of common ret rearrangements using TaqMan reverse-transcription polymerase chain reaction.
- Analysis of radiation-induced copy number variations (gains/losses) using microarray comparative genomic hybridisation (CGH) in cells with ret/PTC chimeric transcripts.
Main Results:
- Four Grays (Gy) of gamma radiation induced ret/PTC-3 rearrangements.
- Ret/PTC-1 transcripts were not detected, suggesting radiation type may influence rearrangement outcomes.
- Array CGH revealed a predominant pattern of subtelomeric deletions in the irradiated cells.
Conclusions:
- Gamma radiation can induce specific ret rearrangements and associated DNA copy number changes in human thyroid epithelial cells.
- The findings suggest chromosome 10 may be a hotspot for radiation-induced DNA damage.
- Further research is needed to understand the underlying mechanisms of radiation-induced thyroid carcinogenesis and non-random genetic alterations.