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

Publication Type:

Journal Article

Source:

Radiation research, Volume 175, Issue 3, p.266-81 (2011)

Keywords:

2011, Adult, Amino Acid Sequence, Animals, Antibodies, Monoclonal, Blood Chemical Analysis, Cell Cycle Proteins, Center-Authored Paper, Chromosomal Proteins, Non-Histone, Clinical Research Division, Comparative Medicine Core Facility, DNA Damage, DNA-Binding Proteins, Dose-Response Relationship, Radiation, Environmental Exposure, Enzyme-Linked Immunosorbent Assay, Female, Humans, Iodine Radioisotopes, LYMPHOCYTES, Male, Molecular Sequence Data, Peptide Fragments, Phosphoproteins, Protein-Serine-Threonine Kinases, Rabbits, Radiometry, Shared Resources, Time Factors, Tumor Suppressor Proteins, Whole-Body Irradiation, Young Adult

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-Smc1(Ser-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-Smc1(Ser-966) in lymphocytes of human patients after therapeutic exposure to ionizing radiation, including total-body irradiation, partial-body irradiation, and internal exposure to (131)I. 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.