[en] In this study, the Whole Human Genome 44K DNA microarray assay was used for the first time to obtain gene expression profiles in human peripheral blood lymphocytes 2 h after exposure (in suspension) to 6.78 MeV mean energy alpha particles from extracellular (211)At. Lymphocytes were exposed to fluences of 0.3-9.6 x 10(6) alpha particles/cm(2) [corresponding to mean absorbed alpha-particle doses (D(alpha)) of 0.05-1.60 Gy] over 30 min. Significantly modulated expression was identified in 338 early-response genes. Up-regulated expression was evident in 183 early-response genes, while the remaining 155 were down-regulated. Over half of the up-regulated genes and 40% of the down-regulated genes had a known biological process related primarily to cell growth and maintenance and cell communication. Genes associated with cell death were found only in the up-regulated genes and those with development only in the down-regulated genes. Eight selected early-response genes that displayed a sustained up- or down-regulation (CD36, HSPA2, MS4A6A, NFIL3, IL1F9, IRX5, RASL11B and SULT1B1) were further validated in alpha-particle-irradiated lymphocytes of two human individuals using the TaqMan(R) RT-qPCR technique. The results confirmed the observed microarray gene expression patterns. The expression modulation profiles of IL1F9, IRX5, RASL11B and SULT1B1 genes demonstrated similar trends in the two individuals studied. However, no significant linear correlation between increasing relative gene expression and the alpha-particle dose was evident. The results suggest the possibility that a panel of genes that react to alpha-particle radiation does exist and that they merit further study in a greater number of individuals to determine their possible value regarding alpha-particle biodosimetry.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Turtoi, Andrei ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
Brown, Ian; UHCW Warwick and University of Cambridge, United Kingdom
Schläger, Martin; Forschungszentrum Juelich, Department of Safety and Radiation Protection, Germany
Schneeweiss, Frank HA; Forschungszentrum Juelich, Department of Safety and Radiation Protection, Germany
Language :
English
Title :
Gene expression profile of human lymphocytes exposed to (211)At alpha particles
Publication date :
August 2010
Journal title :
Radiation Research
ISSN :
0033-7587
Publisher :
Kluge Carden Jennnings Pub Co, Charlottesville, United States - Virginia
S. A. Amundson, K. T. Do, S. Shahab, M. Bittner, P. Meltzer, J. Trent and A. J. Fornace, Identification of potential mRNA biomarkers in peripheral blood lymphocytes for human exposure to ionizing radiation. Radiat. Res. 154, 342-346 (2000).
C. M. Kang, K. P. Park, J. E. Song, D. I. Jeoung, C. K. Cho, T. H. Kim, B. Sangwoo, S. J. Lee and Y. S. Lee, Possible biomarkers for ionizing radiation exposure in human peripheral blood lymphocytes. Radiat. Res. 159, 312-319 (2003).
S. A. Amundson, M. B. Grace, C. B. McLeland, M. W. Epperly, A. Yeager, Q. Zhan, J. S. Greenberger and A. J. Fornace, Human in vivo radiation-induced biomarkers: Gene expression changes in radiotherapy patients. Cancer Res. 64, 6368-6371 (2004).
L. H. Ding, M. Shingyoji, F. Chen, J. J. Hwang, S. Burma, C. Lee, J. F. Cheng and D. J. Chen, Gene expression profiles of normal human fibroblasts after exposure to ionizing radiation: a comparative study of low and high doses. Radiat. Res. 164, 17-26 (2005).
F. Marchetti, M. A. Coleman, I. M. Jones and A. J. Wyrobek, Candidate protein biodosimeters of human exposure to ionizing radiation. Int. J. Radiat. Biol. 82, 605-639 (2006).
A. Turtoi, I. Brown, D. Oskamp and F. H. A. Schneeweiss, Early gene expression in human lymphocytes after gamma-irradiation-a genetic pattern with potential for biodosimetry. Int. J. Radiat. Biol. 84, 375-387 (2008).
A. Turtoi, A. Srivastava, R. N. Sharan, D. Oskamp, R. Hille and F. H. A. Schneeweiss, Early response of lymphocyte proteins after c-radiation. J. Radioanal. Nucl. Chem. 274, 435-439 (2007).
E. A. Blakely, F. Q. H. Ngo, S. B. Curtis and C. A. Tobias, Heavy-ion radiobiology: cellular studies. Adv. Radiat. Biol. 11, 295-389 (1984).
D. T. Goodhead, J. Thacker and R. Cox, Effects of radiation of different qualities on cells: molecular mechanisms of damage repair. Int. J. Radiat. Biol. 63, 543-556 (1993).
J. F. Ward, The complexity of DNA damage: relevance to biological consequences. Int. J. Radiat. Biol. 66, 427-432 (1994).
J. F. Ward, Radiation mutagenesis: the initial DNA lesions responsible. Radiat. Res. 142, 362-368 (1995).
I. Brown, Astatine-211: Its possible application in cancer therapy. Appl. Radiat. Isot. 37, 789-798 (1986).
I. Brown and S. J. Mitchell, The development of a [211At]- astatinated endoradiotherapeutic drug: Part II. Therapeutic results from transplanted adenocarcinoma of the rectum in mice and associated studies. Int. J. Radiat. Oncol. Biol. Phys. 29, 115-124 (1994).
T. Petrich, L. Quintanilla-Martinez, Z. Korkmaz, E. Samson, H. J. Helmeke, G. J. Meyer, W. H. Knapp and E. Pötter, Effective cancer therapy with the a-particle emitter [211At] astatine in a mouse model of genetically modified sodium/iodide symporter-expressing tumors. Clin. Cancer Res. 12, 1342-1348 (2006).
F. H. A. Schneeweiss, R. N. Sharan and I. Brown, At-211-alpha-dose dependence of poly-ADP-ribosylation of human gliobla-stoma cells in vitro-suitability in cancer therapy? Strahlenther. Onkol. 175, 458-461 (1999).
E. I. Azzam, S. M. De Toledo, A. J. Waker and J. B. Little, High and low fluences of a-particles induce a G1 checkpoint in human diploid fibroblasts. Cancer Res. 60, 2623-2631 (2000).
C. Fournier, C. Weise and G. Taucher-Scholz, Accumulation of the cell cycle regulators TP53 and CDKN1A (p21) in human fibroblasts after exposure to low-and high-LET radiation. Radiat. Res. 161, 675-684 (2004).
B. Jakob, M. Scholz and G. Taucher-Scholz, Intermediate localized CDKN1A (p21) radiation response after damage produced by heavy-ion tracks. Radiat. Res. 154, 398-405 (2001).
E. K. Balcer-Kubiczek, X-F. Zhang, G. H. Harrison, X-J. Zhou, R. M. Vigneulle, R. Ove, W. A. McCready and J-F. Xu, Delayed expression of hpS2 and prolonged expression of CIP/WAF1/SD11 in human tumour cells irradiated with X-rays, fission neutrons or 1 GeV/nucleon Fe ions. Int. J. Radiat. Biol. 75, 529-541 (1999).
S. Takahashi, K. Ohnishi, K. Tsuji, H. Matsumoto, H. Aoki, K. Wang, T. Tamamoto, O. Yukawa, Y. Furusawa and T. Ohnishi, WAF1 accumulation by carbon-ion beam and a-particle radiation in human glioblastoma cultured cells. Int. J. Radiat. Biol. 76, 335-341 (2000).
Y. Matsumoto, M. Iwakawa, Y. Furusawa, K. Ishikawa, M. Aoki, K. Imadome, I. Matsumoto, H. Tsujii, K. Ando and T. Imai, Gene expression analysis in human malignant melanoma cell lines exposed to carbon beams. Int. J. Radiat. Biol. 84, 299-314 (2008).
A. Turtoi and F. H. A Schneeweiss, Effect of 211At alpha-particle irradiation on expression of selected radiation responsive genes in human lymphocytes. Int. J. Radiat. Biol. 85, 403-412 (2009).
M. Shehata, J. Schwarzmeier, M. Hilgarth, D. Demirtas, D. Richter, R. Hubmann, P. Boeck, G. Leiner and A. Falkenbach, Effect of combined spa-exercise therapy on circulating TGF-b1 levels in patients with ankylosing spondylitis. Wien. Klin. Wochenschr. 118, 266-272 (2006).
S. A. Ghandhi, B. Yaghoubian and S. A. Amundson, Global gene expression analyses of bystander and alpha particle irradiated normal human lung fibroblasts: synchronous and differential responses. BMC Med. Genomics 1, 63 (2008).
C. Seidl, M. Port, C. Apostolidis, F. Brucherseifer, M. Schwaiger, R. Senekowitsch-Schmidtke and M. Abend, Differential gene expression triggered by highly cytotoxic a-emitter-immunoconjugates in gastric cancer cells. Invest. New Drugs 28, 49-60 (2009).
L. J. Jardine, Decays of astatine-211, polonium-211 and bismuth-207. Phys. Rev. C 11, 1385-1391 (1975).
H. C. Newman, K. M. Prise, M. Folkard and R. D. Michael, DNA double-strand break distributions in X-ray and a-particle irradiated cells: evidence for non-random breakage. Int. J. Radiat. Biol. 71, 347-363 (1997).
E. I. Azzam, S. M. De Toledo and J. B. Little, Expression of CONNEXIN43 is highly sensitive to ionizing radiation and other environmental stresses. Cancer Res. 63, 7128-7135 (2003).
J. X. Li, C. L. Fu, R. Chen, J. Sun, J. H. Nie and J. Tong, Screening of differential expression genes in bone marrow cells of radon-exposed mice. Toxicol. Environ. Health A 70, 964-969 (2007).
J. Soto, C. Sainz, D. González-Lamuño and S. Cos, Low doses of alpha particle irradiation modify the expression of genes regulating apoptosis in human MCF-7 breast cancer cells. Oncol. Rep. 15, 577-581 (2006).
M. H. Roudkenar, L. Li, T. Baba, Y. Kuwahara, H. Nakagawa, L. Wang, S. Kasaoka, Y. Ohkubo, K. Ono and M. Fukumoto, Gene expression profiles in mouse liver cells after exposure to different types of radiation. J. Radiat. Res. (Tokyo) 49, 29-40 (2008).
A. W. Hickman, R. J. Jaramillo, J. F. Lechner and N. F. Johnson, Alpha-particle-induced p53 protein expression in a rat lung epithelial cell strain. Cancer Res. 54, 5797-5800 (1994).
G. E. Woloschak and C-M. Chang-Liu, Differential modulation of specific gene expression following high-and low-LET radiations. Radiat. Res. 124, 183-187 (1991).
E. I. Azzam, S. M. De Toledo, T. Gooding and J. B. Little, Intercellular communication is involved in the bystander regulation of gene expression in human cells exposed to very low fluences of alpha particles. Radiat. Res. 150, 497-504 (1998).
P. K. Narayanan, E. H. Goodwin and B. E. Lehnert, Alpha particles initiate biological production of superoxide anions and hydrogen peroxide in human cells. Cancer Res. 57, 3963-3971 (1997).
P. K. Narayanan, K. E. LaRue, E. H. Goodwin and B. E. Lehnert, Alpha particles induce the production of interleukin-8 by human cells. Radiat. Res. 151, 57-63 (1999).
J. B. Little, E. I. Azzam, S. M. de Toledo and H. Nagasawa, Bystander effects: intercellular transmission of radiation damage signals. Radiat. Prot. Dosimetry 99, 159-162 (2002).