Vol. 27, No. 2, 2005 (June)
	Content

RADIATION-INDUCED DNA-DAMAGE AND GENE EXPRESSION PROFILES IN HUMAN LUNG CANCER CELLS WITH DIFFERENT RADIOSENSITIVITY

Björn Hellman¹, David Brodin², Maria Andersson¹, Karin Dahlman-Wright², Ulf Isacsson³, Daniel Brattström³, Michael Bergqvist³

¹Department of Pharmaceutical Biosciences, Division of Toxicology, Box 594, BMC, Uppsala University, SE-751 24 Uppsala, Sweden
²Department of Biosciences at Novum, Karolinska Institutet, SE-141 57 Huddinge, Sweden
³Department of Oncology, Radiology and Clinical Immunology, University Hospital, SE-751 85 Uppsala, Sweden

Abstract. Background: Measurements of DNA double strand breaks and their subsequent repair after in vitro irradiation has been suggested to be an alternative way of monitoring radiotherapeutic response. Methods: In the present study, the DNA repair kinetics (using a neutral version of the Comet assay) up to 45 min after a single dose of 2 Gy was studied as well as the gene expression profiles, before and 45 min after the irradiation, in two human lung cancer cell lines with different radiosensitivity (U-1285 and U-1810). Results: Immediately after the irradiation, both cell lines responded with increased levels of DNA damage. However, the induced damage was slightly higher in U-1810 (known to be radioresistant) than in U-1285 (known to be radiosensitive), and the latter cell line also seemed to have a slightly more efficient DNA-repair. The two different lung cancer cell lines were highly heterogeneous in gene expression, both before and after the irradiation, and there was no obvious relationship between the Comet data and the microarray data. Conclusion: Given the fact that U-1810 has been classified as radioresistant and U-1285 as radiosensitive in clonogenic assays, the results of the present study indicate that radiation-induced DNA double strand breaks and DNA-repair efficiency are poor indicators of the intrinsic radiosensitivity of human lung cancer cells irradiated with a single dose in vitro.

Key Words: DNA double strand breaks, DNA-repair, Comet assay, DNA damage, response genes, microarray, in vitro irradiation, radioresponsiveness.

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