¹Apoptogen Inc., 401 Smyth Road, Ottawa, Ontario, K1H 8L1, Canada

²Solange Gauthier Karsh Molecular Genetics Laboratory, Children's Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, Ontario, K1H 8L1, Canada

³Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 401 Smyth Road, Ottawa, Ontario, K1H 8L1, Canada

⁴Department of Oncology, McGill University, Montreal, Quebec, H3G 1A4, Canada

Correspondence to: R G Korneluk, Molecular Genetics, Research Institute, Children's Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, Ontario, K1H 8L1, Canada

Inhibitory regulators of apoptosis play a critical role in the responsiveness of tumour cells to cytotoxic agents. The X-linked inhibitor of apoptosis protein (XIAP) is a member of a novel family of Inhibitor of Apoptosis (IAP) proteins. Here we show that acute low dose ionizing irradiation results in the translational upregulation of XIAP that correlates with an increased resistance to radiation in non-small cell lung carcinoma. This upregulation is mediated by an internal ribosome binding mechanism via an IRES element located within a XIAP 5' UTR. Transient overexpression of XIAP rendered human carcinoma cells resistant to low dose -irradiation. By contrast, the antisense targeting of XIAP resulted in increased cell death following irradiation advocating a distinct role for XIAP in radiation resistant phenotype of human cancers. Oncogene (2000) 19, 4174-4177

IAP; radiation induced cell death; IRES; translation