Gene Expression Signatures That Predict Radiation Exposure in Mice and Humans

Overview

Journal PLoS Med

Specialty General Medicine

Date 2007 Apr 5

PMID 17407386

Citations 95

Authors

Holly K Dressman

Garrett G Muramoto

Nelson J Chao

Sarah Meadows

Dawn Marshall

Geoffrey S Ginsburg

Joseph R Nevins

John P Chute

Affiliations

Soon will be listed here.

Abstract

Background: The capacity to assess environmental inputs to biological phenotypes is limited by methods that can accurately and quantitatively measure these contributions. One such example can be seen in the context of exposure to ionizing radiation.

Methods And Findings: We have made use of gene expression analysis of peripheral blood (PB) mononuclear cells to develop expression profiles that accurately reflect prior radiation exposure. We demonstrate that expression profiles can be developed that not only predict radiation exposure in mice but also distinguish the level of radiation exposure, ranging from 50 cGy to 1,000 cGy. Likewise, a molecular signature of radiation response developed solely from irradiated human patient samples can predict and distinguish irradiated human PB samples from nonirradiated samples with an accuracy of 90%, sensitivity of 85%, and specificity of 94%. We further demonstrate that a radiation profile developed in the mouse can correctly distinguish PB samples from irradiated and nonirradiated human patients with an accuracy of 77%, sensitivity of 82%, and specificity of 75%. Taken together, these data demonstrate that molecular profiles can be generated that are highly predictive of different levels of radiation exposure in mice and humans.

Conclusions: We suggest that this approach, with additional refinement, could provide a method to assess the effects of various environmental inputs into biological phenotypes as well as providing a more practical application of a rapid molecular screening test for the diagnosis of radiation exposure.

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References

Hirai Y, Kusunoki Y, Kyoizumi S, Awa A, Pawel D, Nakamura N . Mutant frequency at the HPRT locus in peripheral blood T-lymphocytes of atomic bomb survivors. Mutat Res. 1995; 329(2):183-96. DOI: 10.1016/0027-5107(95)00044-j. View

Falt S, Holmberg K, Lambert B, Wennborg A . Long-term global gene expression patterns in irradiated human lymphocytes. Carcinogenesis. 2003; 24(11):1837-45. DOI: 10.1093/carcin/bgg134. View

Pobel D, Viel J . Case-control study of leukaemia among young people near La Hague nuclear reprocessing plant: the environmental hypothesis revisited. BMJ. 1997; 314(7074):101-6. PMC: 2125632. DOI: 10.1136/bmj.314.7074.101. View

Iwamoto K, Mizuno T, Tokuoka S, Mabuchi K, Seyama T . Frequency of p53 mutations in hepatocellular carcinomas from atomic bomb survivors. J Natl Cancer Inst. 1998; 90(15):1167-8. DOI: 10.1093/jnci/90.15.1167. View

Eisen M, Spellman P, Brown P, Botstein D . Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci U S A. 1998; 95(25):14863-8. PMC: 24541. DOI: 10.1073/pnas.95.25.14863. View

Amundson S, Bittner M, Chen Y, Trent J, Meltzer P, Fornace Jr A . Fluorescent cDNA microarray hybridization reveals complexity and heterogeneity of cellular genotoxic stress responses. Oncogene. 1999; 18(24):3666-72. DOI: 10.1038/sj.onc.1202676. View

Saldanha A . Java Treeview--extensible visualization of microarray data. Bioinformatics. 2004; 20(17):3246-8. DOI: 10.1093/bioinformatics/bth349. View

Patino W, Mian O, Kang J, Matoba S, Bartlett L, Holbrook B . Circulating transcriptome reveals markers of atherosclerosis. Proc Natl Acad Sci U S A. 2005; 102(9):3423-8. PMC: 552911. DOI: 10.1073/pnas.0408032102. View

Lancaster J, Dressman H, Whitaker R, Havrilesky L, Gray J, Marks J . Gene expression patterns that characterize advanced stage serous ovarian cancers. J Soc Gynecol Investig. 2004; 11(1):51-9. DOI: 10.1016/j.jsgi.2003.07.004. View

10.

Chute J, Fung J, Muramoto G, Erwin R . Ex vivo culture rescues hematopoietic stem cells with long-term repopulating capacity following harvest from lethally irradiated mice. Exp Hematol. 2004; 32(3):308-17. DOI: 10.1016/j.exphem.2003.12.002. View

11.

Waselenko J, MacVittie T, Blakely W, Pesik N, Wiley A, Dickerson W . Medical management of the acute radiation syndrome: recommendations of the Strategic National Stockpile Radiation Working Group. Ann Intern Med. 2004; 140(12):1037-51. DOI: 10.7326/0003-4819-140-12-200406150-00015. View

12.

Amundson S, Grace M, McLeland C, Epperly M, Yeager A, Zhan Q . Human in vivo radiation-induced biomarkers: gene expression changes in radiotherapy patients. Cancer Res. 2004; 64(18):6368-71. DOI: 10.1158/0008-5472.CAN-04-1883. View

13.

Hong Y, Stambrook P . Restoration of an absent G1 arrest and protection from apoptosis in embryonic stem cells after ionizing radiation. Proc Natl Acad Sci U S A. 2004; 101(40):14443-8. PMC: 521944. DOI: 10.1073/pnas.0401346101. View

14.

Sankaranarayanan K . Evaluation and re-evaluation of genetic radiation hazards in man. II. The arm number hypothesis and the induction of reciprocal translocations in man. Mutat Res. 1976; 35(3):371-86. DOI: 10.1016/0027-5107(76)90201-3. View

15.

LeMotte P, Little J . A comparison of the lethal effects of intracellular radionuclides in human and rodent cells. Radiat Res. 1983; 95(2):359-69. View

16.

Bender M, Awa A, Brooks A, Evans H, Groer P, Littlefield L . Current status of cytogenetic procedures to detect and quantify previous exposures to radiation. Mutat Res. 1988; 196(2):103-59. DOI: 10.1016/0165-1110(88)90017-6. View

17.

Eguchi-Kasai K, Kosaka T, Sato K, Kaneko I . Reparability of DNA double-strand breaks and radiation sensitivity in five mammalian cell lines. Int J Radiat Biol. 1991; 59(1):97-104. DOI: 10.1080/09553009114550091. View

18.

Neel J, Lewis S . The comparative radiation genetics of humans and mice. Annu Rev Genet. 1990; 24:327-62. DOI: 10.1146/annurev.ge.24.120190.001551. View

19.

Yoshimoto Y, Schull W, Kato H, Neel J . Mortality among the offspring (F1) of atomic bomb survivors, 1946-85. J Radiat Res. 1991; 32(4):327-51. DOI: 10.1269/jrr.32.327. View

20.

Zsebo K, Smith K, Hartley C, Greenblatt M, Cooke K, Rich W . Radioprotection of mice by recombinant rat stem cell factor. Proc Natl Acad Sci U S A. 1992; 89(20):9464-8. PMC: 50152. DOI: 10.1073/pnas.89.20.9464. View