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Novel human radiation exposure biomarker panel applicable for population triage.
Bazan, Jose G; Chang, Polly; Balog, Robert; D'Andrea, Annalisa; Shaler, Thomas; Lin, Hua; Lee, Shirley; Harrison, Travis; Shura, Lei; Schoen, Lucy; Knox, Susan J; Cooper, David E.
Affiliation
  • Bazan JG; Department of Radiation Oncology, Stanford University, Stanford, California.
  • Chang P; SRI International, Menlo Park, California.
  • Balog R; SRI International, Menlo Park, California.
  • D'Andrea A; SRI International, Menlo Park, California.
  • Shaler T; SRI International, Menlo Park, California.
  • Lin H; SRI International, Menlo Park, California.
  • Lee S; SRI International, Menlo Park, California.
  • Harrison T; SRI International, Menlo Park, California.
  • Shura L; Department of Radiation Oncology, Stanford University, Stanford, California.
  • Schoen L; Department of Radiation Oncology, Stanford University, Stanford, California.
  • Knox SJ; Department of Radiation Oncology, Stanford University, Stanford, California.
  • Cooper DE; SRI International, Menlo Park, California. Electronic address: david.cooper@sri.com.
Int J Radiat Oncol Biol Phys ; 90(3): 612-9, 2014 Nov 01.
Article in En | MEDLINE | ID: mdl-25084613
ABSTRACT

PURPOSE:

To identify a panel of radiation-responsive plasma proteins that could be used in a point-of-care biologic dosimeter to detect clinically significant levels of ionizing radiation exposure. METHODS AND MATERIALS Patients undergoing preparation for hematopoietic cell transplantation using radiation therapy (RT) with either total lymphoid irradiation or fractionated total body irradiation were eligible. Plasma was examined from patients with potentially confounding conditions and from normal individuals. Each plasma sample was analyzed for a panel of 17 proteins before RT was begun and at several time points after RT exposure. Paired and unpaired t tests between the dose and control groups were performed. Conditional inference trees were constructed based on panels of proteins to compare the non-RT group with the RT group.

RESULTS:

A total of 151 patients (62 RT, 41 infection, 48 trauma) were enrolled on the study, and the plasma from an additional 24 healthy control individuals was analyzed. In comparison with to control individuals, tenascin-C was upregulated and clusterin was downregulated in patients receiving RT. Salivary amylase was strongly radiation responsive, with upregulation in total body irradiation patients and slight downregulation in total lymphoid irradiation patients compared with control individuals. A panel consisting of these 3 proteins accurately distinguished between irradiated patients and healthy control individuals within 3 days after exposure 97% accuracy, 0.5% false negative rate, 2% false positive rate. The accuracy was diminished when patients with trauma, infection, or both were included (accuracy, 74%-84%; false positive rate, 14%-33%, false negative rate 8%-40%).

CONCLUSIONS:

A panel of 3 proteins accurately distinguishes unirradiated healthy donors from those exposed to RT (0.8-9.6 Gy) within 3 days of exposure. These findings have significant implications in terms of triaging individuals in the case of nuclear or other radiologic events.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Lymphatic Irradiation / Triage / Whole-Body Irradiation / Hematopoietic Stem Cell Transplantation / Tenascin / Point-of-Care Systems / Transplantation Conditioning / Clusterin / Amylases Type of study: Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Adult / Aged / Aged80 / Female / Humans / Male Language: En Journal: Int J Radiat Oncol Biol Phys Year: 2014 Type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Lymphatic Irradiation / Triage / Whole-Body Irradiation / Hematopoietic Stem Cell Transplantation / Tenascin / Point-of-Care Systems / Transplantation Conditioning / Clusterin / Amylases Type of study: Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Adult / Aged / Aged80 / Female / Humans / Male Language: En Journal: Int J Radiat Oncol Biol Phys Year: 2014 Type: Article