title: Correlation of plasma FL expression with bone marrow irradiation dose.
abstract: OBJECTIVE
  Ablative bone marrow irradiation is an integral part of hematopoietic stem cell transplantation. These treatment regimens are based on classically held models of radiation dose and the bone marrow response. Flt-3 ligand (FL) has been suggested as a marker of hematopoiesis and bone marrow status but the kinetics of its response to bone marrow irradiation has yet to be fully characterized. In the current study, we examine plasma FL response to total body and partial body irradiation in mice and its relationship with irradiation dose, time of collection and pattern of bone marrow exposure.
  
  
  METHODS
  C57BL6 mice received a single whole body or partial body irradiation dose of 1-8 Gy. Plasma was collected by mandibular or cardiac puncture at 24, 48 and 72 hr post-irradiation as well as 1-3 weeks post-irradiation. FL levels were determined via ELISA assay and used to generate two models: a linear regression model and a gated values model correlating plasma FL levels with radiation dose.
  
  
  RESULTS
  At all doses between 1-8 Gy, plasma FL levels were greater than control and the level of FL increased proportionally to the total body irradiation dose. Differences in FL levels were statistically significant at each dose and at all time points. Partial body irradiation of the trunk areas, encompassing the bulk of the hematopoietically active bone marrow, resulted in significantly increased FL levels over control but irradiation of only the head or extremities did not. FL levels were used to generate a dose prediction model for total body irradiation. In a blinded study, the model differentiated mice into dose received cohorts of 1, 4 or 8 Gy based on plasma FL levels at 24 or 72 hrs post-irradiation.
  
  
  CONCLUSIONS
  Our findings indicate that plasma FL levels might be used as a marker of hematopoietically active bone marrow and radiation exposure in mice.
authors.affiliation: Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Mary
authors.initials: M
authors.lastname: Sproull
authors.forename: Dane
authors.initials: D
authors.lastname: Avondoglio
authors.forename: Tamalee
authors.initials: T
authors.lastname: Kramp
authors.forename: Uma
authors.initials: U
authors.lastname: Shankavaram
authors.forename: Kevin
authors.initials: K
authors.lastname: Camphausen
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D008565:Membrane Proteins / Q000097:blood*; D051379:Mice; D011829:Radiation Dosage; D013997:Time Factors; D014916:Whole-Body Irradiation
chemical_list: D008565:Membrane Proteins; C084881:flt3 ligand protein