Differential Effects of Alpha-Particle Radiation and X-Irradiation on Genes Associated with Apoptosis

This study examined differential effects of alpha-(α-) particle radiation and X-rays on apoptosis and associated changes in gene expression. Human monocytic cells were exposed to α-particle radiation and X-rays from 0 to 1.5 Gy. Four days postexposure, cell death was measured by flow cytometry and 84 genes related to apoptosis were analyzed using real-time PCR. On average, 33% of the cells were apoptotic at 1.5 Gy of α-particle radiation. Transcript profiling showed statistical expression of 15 genes at all three doses tested. Cells exposed to X-rays were <5% apoptotic at ~1.5 Gy and induced less than a 2-fold expression in 6 apoptotic genes at the higher doses of radiation. Among these 6 genes, Fas and TNF-α were common to the α-irradiated cells. This data suggests that α-particle radiation initiates cell death by TNF-α and Fas activation and through intermediate signalling mediators that are distinct from X-irradiated cells.

[1]  R. Wilkins,et al.  Development and characterization of an in vitro alpha radiation exposure system , 2011, Physics in medicine and biology.

[2]  R. Wakeford Radiation in the workplace—a review of studies of the risks of occupational exposure to ionising radiation , 2009, Journal of radiological protection : official journal of the Society for Radiological Protection.

[3]  J. Valentin,et al.  Nuclear decay data for dosimetric calculations , 2009 .

[4]  H. Walczak,et al.  Death receptors as targets for anti-cancer therapy , 2008, Journal of cellular and molecular medicine.

[5]  M. Hada,et al.  Formation of clustered DNA damage after high-LET irradiation: a review. , 2008, Journal of radiation research.

[6]  K Eckerman,et al.  ICRP Publication 107. Nuclear decay data for dosimetric calculations. , 2008, Annals of the ICRP.

[7]  A. Strasser,et al.  The BCL-2 protein family: opposing activities that mediate cell death , 2008, Nature Reviews Molecular Cell Biology.

[8]  J. Rhim,et al.  Malignant transformation of human benign prostate epithelial cells by high linear energy transfer alpha-particles. , 2007, International journal of oncology.

[9]  H. Werner,et al.  The insulin-like growth factor-I receptor gene: a downstream target for oncogene and tumor suppressor action , 2006, Trends in Endocrinology & Metabolism.

[10]  L. Bohm Inhibition of homologous recombination repair with Pentoxifylline targets G2 cells generated by radiotherapy and induces major enhancements of the toxicity of cisplatin and melphalan given after irradiation , 2006, Radiation oncology.

[11]  S. Cos,et al.  Low doses of alpha particle irradiation modify the expression of genes regulating apoptosis in human MCF-7 breast cancer cells. , 2006, Oncology reports.

[12]  J. Harper,et al.  Induction and quantification of γ-H2AX foci following low and high LET-irradiation , 2006 .

[13]  R Doll,et al.  Radon in homes and risk of lung cancer: collaborative analysis of individual data from 13 European case-control studies , 2004, BMJ : British Medical Journal.

[14]  Won-Jae Kim,et al.  Involvement of mitochondrial- and Fas-mediated dual mechanism in CoCl2-induced apoptosis of rat PC12 cells , 2004, Neuroscience Letters.

[15]  N. Sidhu,et al.  Relative biological effectiveness (RBE) of 210 Po alpha-particles versus X-rays on lethality in bovine endothelial cells , 2003 .

[16]  K. Prise,et al.  Double strand break rejoining after irradiation of human fibroblasts with X rays or alpha particles: PFGE studies and numerical models. , 2002, Radiation protection dosimetry.

[17]  Scott W. Lowe,et al.  Apoptosis A Link between Cancer Genetics and Chemotherapy , 2002, Cell.

[18]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.

[19]  X. Wang The expanding role of mitochondria in apoptosis. , 2001, Genes & development.

[20]  R. Doll,et al.  Radon: a likely carcinogen at all exposures. , 2001, Annals of oncology : official journal of the European Society for Medical Oncology.

[21]  H. Friedmann Health Effects of Exposure to Radon (BEIR VI Report), National Research Council, National Academic Press, Washington DC, ISBN 0-309-05645-4 , 2000 .

[22]  John Calvin Reed Dysregulation of apoptosis in cancer. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[23]  S H Kaufmann,et al.  Mammalian caspases: structure, activation, substrates, and functions during apoptosis. , 1999, Annual review of biochemistry.

[24]  Y. Lazebnik,et al.  Caspases: enemies within. , 1998, Science.

[25]  B. Aggarwal,et al.  Death domain receptors and their role in cell demise. , 1998, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[26]  E. Wright Radiation-induced genomic instability in haemopoietic cells. , 1998, International journal of radiation biology.

[27]  C. Reutelingsperger,et al.  Annexin V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure. , 1998, Cytometry.

[28]  D. Leroith,et al.  Insulin-like Growth Factor 1 Inhibits Apoptosis Using the Phosphatidylinositol 3′-Kinase and Mitogen-activated Protein Kinase Pathways* , 1997, The Journal of Biological Chemistry.

[29]  P. Nicotera,et al.  Radiation induced apoptosis. , 1996, Mutation research.

[30]  D. Goeddel,et al.  The TNF receptor 1-associated protein TRADD signals cell death and NF-κB activation , 1995, Cell.

[31]  D. Hockenbery Defining apoptosis. , 1995, The American journal of pathology.

[32]  D T Goodhead,et al.  Initial events in the cellular effects of ionizing radiations: clustered damage in DNA. , 1994, International journal of radiation biology.

[33]  J Salvage,et al.  A matter of life and death. , 1981, Nursing times.