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Carcinogenesis Advance Access published online on September 1, 2003
Carcinogenesis, doi:10.1093/carcin/bgg134
© 2003 by Oxford University Press
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© 2003 Oxford University Press

CARCINOGENESIS

Long-term global gene expression patterns in irradiated human lymphocytes

Susann Fält 1*, Kerstin Holmberg 2, Bo Lambert 1, and Anders Wennborg 1

1 Unit of Environmental Medicine, Center for Nutrition and Toxicology, Department of Biosciences at Novum, Karolinska Institutet, S-14157 Huddinge, Sweden
2 Unit of Environmental Medicine, Center for Nutrition and Toxicology, Department of Biosciences at Novum, Karolinska Institutet, S-14157 Huddinge, Sweden; Department of Clinical Genetics Karolinska Hospital, S-17176 Stockholm, Sweden

* Corresponding author. E-mail: susann.falt{at}cnt.ki.se.

Received 23 May 2003 ; revised 8 July 2003 ; accepted 25 July 2003

Abstract

Radiation-induced chromosomal instability has many features in common with genomic instability of cancer cells. In order to understand the delayed cellular response to ionising radiation we have studied variations in the patterns of gene expression in primary human lymphocytes at various time points after gamma irradiation in vitro. Cells either exposed to 3 Gy of gamma rays in vitro or unexposed were subjected to long-term growth in bulk culture or as individual T-cell clones. Samples were taken at day 7, 17 or 55 from bulk cultures. The T-cell clones were harvested after 22-46 days. Total RNA was used to generate cDNA probes for hybridisation to oligonucleotide arrays containing 12 625 gene templates (Affymetrix). The results showed that: (1) Irradiation as well as culture time influence the gene expression patterns, (2) The number of genes with increased or decreased expression in irradiated cells increases dramatically with increasing culture time, (3) The changes of gene expression showed a significantly more diversified pattern in the irradiated T-cell clones than in non-irradiated clones. We conclude that the diversification of the transcriptome associated with radiation exposure reflects subtle changes of expression in many genes, rather than being the result of major changes in a few genes. Finally, (4) we sorted out a set of genes whose change of expression correlates with radiation exposure in both bulk cultures and T-cell clones. Very few of these genes overlap with genes that change during the acute response to radiation. This set of genes may be regarded as a starting point for further studies of the cellular phenotype associated with radiation-induced genomic instability.

Gene expression, lymphocytes, irradiation
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