title: Radiation-induced changes in levels of selected proteins in peripheral blood serum of breast cancer patients as a potential triage biodosimeter for large-scale radiological emergencies.
abstract: The threat of a large scale radiological emergency, where thousands of people may require fast biological dosimetry for the purpose of triage, makes it necessary to search for new, high throughput biological dosimeters. The authors tested an assay based on the quantitative analysis of selected proteins in peripheral blood serum. They were particularly interested in testing proteins that are specific to irradiation of skin, as these can be used in cases of partial body exposure. Candidate proteins were identified in an earlier study with mice, where skin of the animals was exposed to different doses of radiation and global expression of serum proteins was analyzed. Eight proteins were found, the expression of which showed a consistent dose-response relationship. Human analogues of these proteins were identified, and their expression was measured in peripheral blood serum of 16 breast cancer patients undergoing external beam radiotherapy. The proteins were Apolipoprotein E; Apolipoprotein H; Complement protein 7; Prothrombinase; Pantothenate Kinase 4; Alpha-2-macroglobulin; Fetuin B and Alpha-1-Anti-Chymotrypsin. Measurements were carried out in blood samples collected prior to exposure (control), on the day after one fraction (2 Gy), on the day after five fractions (10 Gy), on the day after 10 fractions (20 Gy), and 1 mo after 23-25 fractions (total dose of 46-50 Gy). Multivariate analysis was carried out, and a multinomial logistic regression model was built. The results indicate that the combined analysis of Apolipoprotein E, Factor X, and Pantothenate Kinase 4 allows discriminating between exposure to 2 Gy and lower and between 10 Gy and higher. The discrimination is possible up to 1 mo after exposure.
authors.affiliation: *CRPR, Stockholm University, Sweden; Institute of Mother and Child, Warszawa, Poland; †CRPR Stockholm University Sweden; Faculty of Medicine, University of Latvia; ‡Data Mining Group, Institute of Automatic Control, Silesian University of Technology, Gliwice, Poland; §Division of Radiotherapy, Radiumhemmet, Karolinska University Hospital, Stockholm, Sweden; **Public Health England Centre for Radiation, Chemical and Environmental Hazards, Chilton, Didcot, Oxford; ††Institute for Radiological Protection and Nuclear Safety, France; ‡‡CRPR, Stockholm University, Sweden; §§CRPR, Stockholm University, Sweden; Jan Kochanowski University, Kielce, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Deperas-Kaminska
authors.forename: Ainars
authors.initials: A
authors.lastname: Bajinskis
authors.forename: Michal
authors.initials: M
authors.lastname: Marczyk
authors.forename: Joanna
authors.initials: J
authors.lastname: Polanska
authors.forename: Peter
authors.initials: P
authors.lastname: Wersäll
authors.forename: Elisabet
authors.initials: E
authors.lastname: Lidbrink
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Ainsbury
authors.forename: Oliver
authors.initials: O
authors.lastname: Guipaud
authors.forename: Marc
authors.initials: M
authors.lastname: Benderitter
authors.forename: Siamak
authors.initials: S
authors.lastname: Haghdoost
authors.forename: Andrzej
authors.initials: A
authors.lastname: Wojcik
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis*; D001798:Blood Proteins / Q000032:analysis*; D001943:Breast Neoplasms / Q000097:blood* / Q000532:radiotherapy; D004307:Dose-Response Relationship, Radiation; D004630:Emergencies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D051379:Mice; D011832:Radiation Injuries / Q000097:blood / Q000175:diagnosis*; D011834:Radiation Monitoring / Q000379:methods*; D011874:Radiometry; D014218:Triage / Q000379:methods
chemical_list: D015415:Biomarkers; D001798:Blood Proteins