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DNA Damage and Cellular Stress Responses

ATM Requirement in Gene Expression Responses to Ionizing Radiation in Human Lymphoblasts and Fibroblasts

¹ Growth Control and Cancer Group, and ² National Institute of Environmental Health Sciences Microarray Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina; ³ Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina

Requests for reprints: Richard S. Paules, Growth Control and Cancer Group, National Institute of Environmental Health Sciences, PO Box 12233, MD D2-03, Research Triangle Park, NC 27709. Phone: 919-541-3710; Fax: 919-316-4771. E-mail: paules{at}niehs.nih.gov.

The heritable disorder ataxia telangiectasia (AT) is caused by mutations in the AT-mutated (ATM) gene with manifestations that include predisposition to lymphoproliferative cancers and hypersensitivity to ionizing radiation (IR). We investigated gene expression changes in response to IR in human lymphoblasts and fibroblasts from seven normal and seven AT-affected individuals. Both cell types displayed ATM-dependent gene expression changes after IR, with some responses shared and some responses varying with cell type and dose. Interestingly, after 5 Gy IR, lymphoblasts displayed ATM-independent responses not seen in the fibroblasts at this dose, which likely reflect signaling through ATM-related kinases, e.g., ATR, in the absence of ATM function. (Mol Cancer Res 2006;4(3):197–207)

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