title: Accelerated hematopoietic toxicity by high energy (56)Fe radiation.
abstract: OBJECTIVE
  There is little information on the relative toxicity of highly charged (Z) high-energy (HZE) radiation in animal models compared to γ or X-rays, and the general assumption based on in vitro studies has been that acute toxicity is substantially greater.
  
  
  METHODS
  C57BL/6J mice were irradiated with (56)Fe ions (1 GeV/nucleon), and acute (within 30 d) toxicity compared to that of γ rays or protons (1 GeV). To assess relative hematopoietic and gastrointestinal toxicity, the effects of (56)Fe ions were compared to γ rays using complete blood count (CBC), bone marrow granulocyte-macrophage colony forming unit (GM-CFU), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay for apoptosis in bone marrow, and intestinal crypt survival.
  
  
  RESULTS
  Although onset was more rapid, (56)Fe ions were only slightly more toxic than γ rays or protons with lethal dose (LD)(50/30) (a radiation dose at which 50% lethality occurs at 30-day) values of 5.8, 7.25, and 6.8 Gy, respectively, with relative biologic effectiveness for (56)Fe ions of 1.25 and 1.06 for protons.
  
  
  CONCLUSIONS
  (56)Fe radiation caused accelerated and more severe hematopoietic toxicity. Early mortality correlated with more profound leukopenia and subsequent sepsis. Results indicate that there is selective enhanced toxicity to bone marrow progenitor cells, which are typically resistant to γ rays, and bone marrow stem cells, because intestinal crypt cells did not show increased HZE toxicity.
authors.affiliation: Department of Biochemistry and Molecular & Cell Biology and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057-1468, USA.
authors.forename: Kamal
authors.initials: K
authors.lastname: Datta
authors.forename: Shubhankar
authors.initials: S
authors.lastname: Suman
authors.forename: Daniela
authors.initials: D
authors.lastname: Trani
authors.forename: Kathryn
authors.initials: K
authors.lastname: Doiron
authors.forename: Jimmy A
authors.initials: JA
authors.lastname: Rotolo
authors.forename: Bhaskar V S
authors.initials: BV
authors.lastname: Kallakury
authors.forename: Richard
authors.initials: R
authors.lastname: Kolesnick
authors.forename: Michael F
authors.initials: MF
authors.lastname: Cole
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Fornace
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000150:complications / Q000209:etiology; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects; D041981:Gastrointestinal Tract / Q000528:radiation effects; D063193:Heavy Ion Radiotherapy; D006410:Hematopoiesis / Q000528:radiation effects*; D007501:Iron / Q000737:chemistry* / Q000633:toxicity*; D007970:Leukopenia / Q000150:complications / Q000209:etiology; D018499:Linear Energy Transfer / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D011522:Protons / Q000009:adverse effects; D012062:Relative Biological Effectiveness; D013997:Time Factors; D014916:Whole-Body Irradiation
chemical_list: D011522:Protons; D007501:Iron
references.citation: Int J Radiat Biol. 2011 Jan;87(1):8-23
references.pmid: 21067301
references.citation: Proc Natl Acad Sci U S A. 1999 Sep 14;96(19):10863-8
references.pmid: 10485917
references.citation: Radiother Oncol. 1997 Mar;42(3):303-9
references.pmid: 9155083
references.citation: Radiat Res. 2004 Jun;161(6):648-55
references.pmid: 15161355
references.citation: Z Med Phys. 2008;18(4):276-85
references.pmid: 19205297
references.citation: Radiat Environ Biophys. 2010 Aug;49(3):389-96
references.pmid: 20490531
references.citation: Int J Radiat Biol Relat Stud Phys Chem Med. 1970;17(3):261-7
references.pmid: 4912514
references.citation: Mil Med. 2004 Mar;169(3):194-7
references.pmid: 15080238
references.citation: Am J Physiol Regul Integr Comp Physiol. 2002 Mar;282(3):R677-88
references.pmid: 11832386
references.citation: Nat Genet. 1999 Oct;23(2):176-84
references.pmid: 10508513
references.citation: Radiat Res. 2008 Feb;169(2):149-61
references.pmid: 18220468
references.citation: Radiat Res. 2003 Oct;160(4):425-35
references.pmid: 12968931
references.citation: Adv Space Res. 1992;12(2-3):407-16
references.pmid: 11537038
references.citation: Phys Med. 2001;17 Suppl 1:183-4
references.pmid: 11776254
references.citation: Semin Radiat Oncol. 2006 Oct;16(4):249-59
references.pmid: 17010908
references.citation: Adv Space Res. 1986;6(11):153-65
references.pmid: 11537215
references.citation: Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10569-74
references.pmid: 16024726
references.citation: Acta Haematol. 1981;66(4):226-32
references.pmid: 6800187
references.citation: Radiat Res. 2010 Jun;173(6):729-37
references.pmid: 20518652
references.citation: Radiat Res. 2009 Apr;171(4):474-83
references.pmid: 19397448
references.citation: Oncogene. 2004 Apr 22;23(19):3265-71
references.pmid: 15064735
references.citation: Radiat Res. 2001 Feb;155(2):353-9
references.pmid: 11175671
references.citation: Mil Med. 2002 Feb;167(2 Suppl):105-6
references.pmid: 11873487
references.citation: Int J Radiat Oncol Biol Phys. 2009 Jan 1;73(1):6-8
references.pmid: 19100919
references.citation: Int J Radiat Biol. 2010 May;86(5):409-19
references.pmid: 20397846
references.citation: Radiat Res. 2006 Feb;165(2):223-30
references.pmid: 16435920