Advertisement
Review Article| Volume 26, ISSUE 2, P491-504, June 2006

Modulating Radiation Resistance: Insights Based on Defenses Against Reactive Oxygen Species in the Radioresistant Bacterium Deinococcus radiodurans

      Humans and other mammals are remarkably sensitive to acute doses of ionizing radiation (IR) (eg, x and γ rays, neutrons, and α and β particles) [
      • von Sonntag C.
      The chemical basis of radiation biology.
      ], in that a whole-body exposure of just 5 Gy is lethal; the gray (Gy) is the amount of energy absorbed by a tissue or substance and applies to all types of radiation. Low-dose chronic IR is a well-established human carcinogen and is omnipresent on Earth. Background sources of terrestrial IR include radioisotopes present in essentially all materials in the environment and cosmic sources, including the sun and extremely distant galactic events, such as supernovae. Collectively, these natural sources of IR deliver only about 0.0024 Gy/y [
      • Sorenson J.A.
      Perception of radiation hazards.
      ]. In this context, the evolution of bacteria that are able to grow under high-dose chronic IR (60 Gy/h) [
      • Brim H.
      • McFarlan S.C.
      • Fredrickson J.K.
      • et al.
      Engineering Deinococcus radiodurans for metal remediation in radioactive mixed waste environments.
      ] or survive acute irradiation exposures [
      • Daly M.J.
      • Ling O.
      • Fuchs P.
      • et al.
      In vivo damage and recA-dependent repair of plasmid and chromosomal DNA in the radiation-resistant bacterium Deinococcus radiodurans.
      ] of 15,000 Gy is truly extraordinary given the apparent absence of highly radioactive habitats on Earth over geologic times. Human-made sources of IR, developed over the last 60 years, have contributed significantly to low-dose radiation, including occupational exposures associated with developing and maintaining nuclear weaponry and power sources; environmental release of radionuclides, such as occurred during atomic bomb tests during the Cold War (1945–1986); and nuclear power plant accidents, such as in Chernobyl, Ukraine (1986) [
      • Dubrova Y.E.
      Long-term genetic effects of radiation exposure.
      ]. A recent National Research Council report [
      • National Research Council
      Health risks from exposure to low levels of ionizing radiation. BEIR VII Phase 2.
      ] concluded that whereas risks of low-dose IR are small, there is no safe level. This finding has grown stronger over the last 15 years, dismissing the notion that there is a threshold of exposure to IR below which there is no health threat. Currently, the most significant, widespread human-made sources of IR are medical devices and procedures, including diagnostic radiographs and therapeutic radiation. Natural background IR remains the most significant source of exposure for humans, however, representing more than 80% of the total dose of a typical resident of the United States [
      • National Research Council
      Health risks from exposure to low levels of ionizing radiation. BEIR VII Phase 2.
      ]. Although the biological hazards of IR have been evident for a century [
      • von Sonntag C.
      The chemical basis of radiation biology.
      ], a clear understanding of the molecular mechanisms underlying IR toxicity and resistance remains controversial despite decades of molecular research dedicated to this field. Perhaps paramount, the catastrophic terrorist events of September 11, 2001 underscore the possibility of radiological terrorism and the pressing need to understand further how to prevent radiation injury. This article presents a new view of IR-resistance mechanisms in extremely radiation-resistant bacteria and questions some longstanding assumptions regarding the causes of IR toxicity. The extrapolation of recent experimental findings [
      • Daly M.J.
      • Gaidamakova E.K.
      • Matrosova V.Y.
      • et al.
      Accumulation of Mn(II) in Deinococcus radiodurans facilitates gamma-radiation resistance.
      ] to the potential development of approaches to modulate radiation resistance is intentionally speculative, aimed at contributing to the groundwork of new ideas needed to address the emerging threat of nuclear terrorism.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribers receive full online access to your subscription and archive of back issues up to and including 2002.

      Content published before 2002 is available via pay-per-view purchase only.

      Subscribe:

      Subscribe to Clinics in Laboratory Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • von Sonntag C.
        The chemical basis of radiation biology.
        Taylor & Francis, London1987
        • Sorenson J.A.
        Perception of radiation hazards.
        Semin Nucl Med. 1986; 16: 158-170
        • Brim H.
        • McFarlan S.C.
        • Fredrickson J.K.
        • et al.
        Engineering Deinococcus radiodurans for metal remediation in radioactive mixed waste environments.
        Nat Biotechnol. 2000; 18: 85-90
        • Daly M.J.
        • Ling O.
        • Fuchs P.
        • et al.
        In vivo damage and recA-dependent repair of plasmid and chromosomal DNA in the radiation-resistant bacterium Deinococcus radiodurans.
        J Bacteriol. 1994; 176: 3508-3517
        • Dubrova Y.E.
        Long-term genetic effects of radiation exposure.
        Mutat Res. 2003; 544: 433-439
        • National Research Council
        Health risks from exposure to low levels of ionizing radiation. BEIR VII Phase 2.
        The National Academies Press, Washington, DC2005
        • Daly M.J.
        • Gaidamakova E.K.
        • Matrosova V.Y.
        • et al.
        Accumulation of Mn(II) in Deinococcus radiodurans facilitates gamma-radiation resistance.
        Science. 2004; 306: 1025-1028
        • Lea D.E.
        Actions of radiation on living cells.
        University Press, Cambridge, MA1946
        • Ghosal D.
        • Omelchenko M.V.
        • Gaidamakova E.K.
        • et al.
        How radiation kills cells: survival of Deinococcus radiodurans and Shewanella oneidensis under oxidative stress.
        FEMS Microbiol Rev. 2005; 29: 361-375
        • Thornley M.J.
        Radiation resistance among bacteria.
        J Appl Bacteriol. 1963; 26: 334-345
        • Qiu X.
        • Daly M.J.
        • Vasilenko A.
        • et al.
        Transcriptome analysis applied to survival of Shewanella oneidensis MR-1 exposed to ionizing radiation.
        J Bacteriol. 2006; 188: 1199-1204
        • Du J.
        • Gebicki J.M.
        Proteins are major initial cell targets of hydroxyl free radicals.
        Int J Biochem Cell Biol. 2004; 36: 2334-2343
        • Nauser T.
        • Koppenol W.H.
        • Gebicki J.M.
        The kinetics of oxidation of GSH by protein-bound radicals.
        Biochem J. 2005; 392: 693-701
      1. Bystander effects and the dose response, Belle Newsletter Vol. 11, No. 3, October 2003. Available at: http://www.belleonline.com/newsletters/volume11/vol11-3.pdf. Accessed November 20, 2005.

        • Van Gerwen S.J.
        • Rombouts F.M.
        • van't Riet K.
        • et al.
        A data analysis of the irradiation parameter D10 for bacteria and spores under various conditions.
        J Food Prot. 1999; 62: 1024-1032
        • Billi D.
        • Friedmann E.I.
        • Hofer K.G.
        • et al.
        Ionizing-radiation resistance in the desiccation-tolerant cyanobacterium Chroococcidiopsis.
        Appl Environ Microbiol. 2000; 66: 1489-1492
        • Leibowitz P.J.
        • Schwartzberg L.S.
        • Bruce A.K.
        The in vivo association of manganese with the chromosome of Micrococcus radiodurans.
        Photochem Photobiol. 1976; 23: 45-50
        • Merrick T.P.
        • Bruce A.K.
        Radiation response of potassium efflux in Micrococcus radiodurans and Sarcina lutea.
        Radiat Res. 1965; 24: 612-618
        • Omelchenko M.V.
        • Wolf Y.I.
        • Gaidamakova E.K.
        • et al.
        Comparative genomics of Thermus thermophilus HB27 and Deinococcus radiodurans R1: Divergent paths of adaptation to thermophily and radiation resistance.
        BMC Evol Biol. 2005; 5: 57
        • Gerard E.
        • Jolivet E.
        • Prieur D.
        • et al.
        DNA protection mechanisms are not involved in the radioresistance of the hyperthermophilic archaea Pyrococcus abyssi and P. furiosus.
        Mol Genet Genomics. 2001; 266: 72-78
        • Tanaka M.
        • Earl A.M.
        • Howell H.A.
        • et al.
        Analysis of Deinococcus radiodurans's transcriptional response to ionizing radiation and desiccation reveals novel proteins that contribute to extreme radioresistance.
        Genetics. 2004; 168: 21-33
        • Liu Y.
        • Zhou J.
        • Omelchenko M.V.
        • et al.
        Transcriptome dynamics of Deinococcus radiodurans recovering from ionizing radiation.
        Proc Natl Acad Sci USA. 2003; 100: 4191-4196
        • Harris D.R.
        • Tanaka M.
        • Saveliev S.V.
        • et al.
        Preserving genome integrity: the DdrA protein of Deinococcus radiodurans R1.
        PLoS Biol. 2004; 2: 304-313
      2. Gaidamakova EK, Matrosova VY, Zhai M, et al. Resistance phenotypes of novel Deinococcus radiodurans mutants. 2005. Available at: http://www.usuhs.mil/pat/deinococcus/index_20.htm. Accessed November 22, 2005.

        • Minton K.W.
        Repair of ionizing-radiation damage in the radiation resistant bacterium Deinococcus radiodurans.
        Mutat Res. 1996; 363: 1-7
        • Heitman J.
        • Zinder N.D.
        • Model P.
        Repair of the Escherichia coli chromosome after in vivo scission by the EcoRI endonuclease.
        Proc Natl Acad Sci USA. 1989; 86: 2281-2285
        • Daly M.J.
        • Minton K.W.
        Interchromosomal recombination in the extremely radioresistant bacterium Deinococcus radiodurans.
        J Bacteriol. 1995; 177: 5495-5505
        • Daly M.J.
        • Minton K.W.
        An alternative pathway of recombination of chromosomal fragments precedes recA-dependent recombination in the radioresistant bacterium Deinococcus radiodurans.
        J Bacteriol. 1996; 178: 4461-4471
        • Daly M.J.
        • Minton K.W.
        Recombination between a resident plasmid and the chromosome following irradiation of the radioresistant bacterium Deinococcus radiodurans.
        Gene. 1997; 187: 225-229
        • Eltsov M.
        • Dubochet J.
        Fine structure of the Deinococcus radiodurans nucleoid revealed by cryoelectron microscopy of vitreous sections.
        J Bacteriol. 2005; 187: 8047-8054
        • Archibald F.S.
        • Fridovich I.
        The scavenging of superoxide radical by manganous complexes: in vitro.
        Arch Biochem Biophys. 1982; 214: 452-463
        • Imlay J.A.
        Pathways of oxidative damage.
        Annu Rev Microbiol. 2003; 57: 395-418
        • Liochev S.I.
        • Fridovich I.
        Cross-compartment protection by SOD1.
        Free Radic Biol Med. 2005; 38: 146-147
        • Lin L.H.
        • Slater G.F.
        • Lollar B.S.
        • et al.
        The yield and isotopic composition of radiolytic H2, a potential energy source for the deep subsurface biosphere.
        Geochim Cosmochim Acta. 2004; 69: 893-903
        • Venkateswaran A.
        • McFarlan S.C.
        • Ghosal D.
        • et al.
        Physiologic determinants of radiation resistance in Deinococcus radiodurans.
        Appl Environ Microbiol. 2000; 66: 2620-2626
        • Wolters H.
        • Konings A.W.T.
        Radiation effects on membranes. III. The effect of X irradiation on survival of mammalian cells substituted by polyunsaturated fatty acids.
        Radiat Res. 1982; 92: 474-482
        • Wolf Y.I.
        • Koonin E.V.
        Origin of an animal mitochondrial DNA polymerase subunit via lineage-specific acquisition of a glycyl-tRNA synthetase from bacteria of the Thermus-Deinococcus group.
        Trends Genet. 2001; 17: 431-433
        • Belyakov O.V.
        • Mitchell S.A.
        • Parikh D.
        • et al.
        Biological effects in unirradiated human tissue induced by radiation damage up to 1 mm away.
        Proc Natl Acad Sci USA. 2005; 102: 14203-14208
        • Azzam E.I.
        • De Toledo S.M.
        • Spitz D.R.
        • et al.
        Oxidative metabolism modulates signal transduction and micronucleus formation in bystander cells from alpha-particle-irradiated normal human fibroblast cultures.
        Cancer Res. 2002; 62: 5436-5442
        • Leach J.K.
        • Van Tuyle G.
        • Lin P.S.
        • et al.
        Ionizing radiation-induced, mitochondria-dependent generation of reactive oxygen/nitrogen.
        Cancer Res. 2001; 61: 3894-3901
        • Gudz T.I.
        • Pandelova I.G.
        • Novgorodov S.A.
        Stimulation of respiration in rat thymocytes induced by ionizing radiation.
        Radiat Res. 1994; 138: 114-120
        • Bruce A.K.
        • Berner J.D.
        Respiratory activity as a determinant of radiation survival response.
        Can J Microbiol. 1976; 22: 1336-1344
        • Puskin J.S.
        • Gunter T.E.
        Ion and pH gradients across the transport membrane of mitochondria following Mn ++ uptake in the presence of acetate.
        Biochem Biophys Res Commun. 1973; 51: 797-803
        • Gunter T.E.
        • Miller L.M.
        • Gavin C.E.
        • et al.
        Determination of the oxidation states of manganese in brain, liver, and heart mitochondria.
        J Neurochem. 2004; 88: 266-280
        • Sohal R.S.
        • Dubey A.
        Mitochondrial oxidative damage, hydrogen peroxide release, and aging.
        Free Radic Biol Med. 1994; 16: 621-626
        • Cotrim A.P.
        • Sowers A.L.
        • Lodde B.M.
        • et al.
        Kinetics of tempol for prevention of xerostomia following head and neck irradiation in a mouse model.
        Clin Cancer Res. 2005; 11: 7564-7568
        • Lee J.H.
        • Lee Y.M.
        • Park J.W.
        Regulation of ionizing radiation-induced apoptosis by a manganese porphyrin complex.
        Biochem Biophys Res Commun. 2005; 334: 298-305
        • Metz J.M.
        • Smith D.
        • Mick R.
        • et al.
        A phase I study of topical Tempol for the prevention of alopecia induced by whole brain radiotherapy.
        Clin Cancer Res. 2004; 10: 6411-6417
        • Mizak L.
        • Mierzejewski J.
        Gamma radiation resistance of Bacillus anthracis spores.
        Med Dosw Mikrobiol. 2003; 55 ([Polish.]): 315-323
        • Daly M.J.
        The emerging impact of genomics on the development of biological weapons. Threats and benefits posed by engineered extremophiles.
        Clin Lab Med. 2001; 21: 619-629