Blood-based detection of radiation exposure in humans based on novel phospho-Smc1 ELISA

Richard G. Ivey, Heather D. Moore, Uliana J. Voytovich, Cortlandt P. Thienes, Travis D. Lorentzen, Era L. Pogosova-Agadjanyan, Shani Frayo, Venissa K. Izaguirre, Sally J. Lundberg, Lacey Hedin, Kas Ray Badiozamani, Andrew N. Hoofnagle, Derek L. Stirewalt, Pei Wang, George E. Georges, Ajay K. Gopal, Amanda G. Paulovich

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

The structural maintenance of chromosome 1 (Smc1) protein is a member of the highly conserved cohesin complex and is involved in sister chromatid cohesion. In response to ionizing radiation, Smc1 is phosphorylated at two sites, Ser-957 and Ser-966, and these phosphorylation events are dependent on the ATM protein kinase. In this study, we describe the generation of two novel ELISAs for quantifying phospho-Smc1Ser-957 and phospho-Smc1 Ser-966. Using these novel assays, we quantify the kinetic and biodosimetric responses of human cells of hematological origin, including immortalized cells, as well as both quiescent and cycling primary human PBMC. Additionally, we demonstrate a robust in vivo response for phospho-Smc1 Ser-957 and phospho-Smc1Ser-966 in lymphocytes of human patients after therapeutic exposure to ionizing radiation, including total-body irradiation, partial-body irradiation, and internal exposure to 131I. These assays are useful for quantifying the DNA damage response in experimental systems and potentially for the identification of individuals exposed to radiation after a radiological incident.

Original languageEnglish (US)
Pages (from-to)266-281
Number of pages16
JournalRadiation Research
Volume175
Issue number3
DOIs
StatePublished - Mar 2011

ASJC Scopus subject areas

  • Radiation
  • Biophysics
  • Radiology Nuclear Medicine and imaging

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