title: Relative Biological Effectiveness of Energetic Heavy Ions for Intestinal Tumorigenesis Shows Male Preponderance and Radiation Type and Energy Dependence in APC(1638N/+) Mice.
abstract: OBJECTIVE
  There are uncertainties associated with the prediction of colorectal cancer (CRC) risk from highly energetic heavy ion (HZE) radiation. We undertook a comprehensive assessment of intestinal and colonic tumorigenesis induced after exposure to high linear energy transfer (high-LET) HZE radiation spanning a range of doses and LET in a CRC mouse model and compared the results with the effects of low-LET γ radiation.
  
  
  METHODS
  Male and female APC(1638N/+) mice (n=20 mice per group) were whole-body exposed to sham-radiation, γ rays, (12)C, (28)Si, or (56)Fe radiation. For the >1 Gy HZE dose, we used γ-ray equitoxic doses calculated using relative biological effectiveness (RBE) determined previously. The mice were euthanized 150 days after irradiation, and intestinal and colon tumor frequency was scored.
  
  
  RESULTS
  The highest number of tumors was observed after (28)Si, followed by (56)Fe and (12)C radiation, and tumorigenesis showed a male preponderance, especially after (28)Si. Analysis showed greater tumorigenesis per unit of radiation (per cGy) at lower doses, suggesting either radiation-induced elimination of target cells or tumorigenesis reaching a saturation point at higher doses. Calculation of RBE for intestinal and colon tumorigenesis showed the highest value with (28)Si, and lower doses showed greater RBE relative to higher doses.
  
  
  CONCLUSIONS
  We have demonstrated that the RBE of heavy ion radiation-induced intestinal and colon tumorigenesis is related to ion energy, LET, gender, and peak RBE is observed at an LET of 69 keV/μm. Our study has implications for understanding risk to astronauts undertaking long duration space missions.
authors.affiliation: Department of Biochemistry and Molecular & Cellular Biology and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia.
authors.forename: Shubhankar
authors.initials: S
authors.lastname: Suman
authors.affiliation: Department of Biochemistry and Molecular & Cellular Biology and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia.
authors.forename: Santosh
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Biochemistry and Molecular & Cellular Biology and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia.
authors.forename: Bo-Hyun
authors.initials: BH
authors.lastname: Moon
authors.affiliation: Department of Biochemistry and Molecular & Cellular Biology and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia.
authors.forename: Steve J
authors.initials: SJ
authors.lastname: Strawn
authors.affiliation: Department of Biochemistry and Molecular & Cellular Biology and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia.
authors.forename: Hemang
authors.initials: H
authors.lastname: Thakor
authors.affiliation: Department of Biochemistry and Molecular & Cellular Biology and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia.
authors.forename: Ziling
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Department of Cell Biology, UT Southwestern Medical Center, Dallas, Texas.
authors.forename: Jerry W
authors.initials: JW
authors.lastname: Shay
authors.affiliation: Department of Biochemistry and Molecular & Cellular Biology and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia; Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Fornace
authors.affiliation: Department of Biochemistry and Molecular & Cellular Biology and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia. Electronic address: kd257@georgetown.edu.
authors.forename: Kamal
authors.initials: K
authors.lastname: Datta
mesh_terms: D000818:Animals; D002244:Carbon / Q000009:adverse effects / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000209:etiology; D005260:Female; D005296:Ferrous Compounds / Q000009:adverse effects / Q000627:therapeutic use; D005720:Gamma Rays / Q000009:adverse effects* / Q000627:therapeutic use; D063193:Heavy Ion Radiotherapy / Q000009:adverse effects* / Q000379:methods; D007414:Intestinal Neoplasms / Q000209:etiology*; D007421:Intestine, Small / Q000528:radiation effects; D018499:Linear Energy Transfer; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009381:Neoplasms, Radiation-Induced / Q000209:etiology*; D011879:Radiotherapy Dosage; D012062:Relative Biological Effectiveness; D012737:Sex Factors; D012825:Silicon / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D005296:Ferrous Compounds; D002244:Carbon; D012825:Silicon