A Validated High-Let Radiation Specific Biomarker in the Mayak Worker Cohort

David J. Brenner, Ph.D., D.Sc. ; Tamara Azizova, M.D.

Columbia University. Trustees.

关键词: Body Burden;    Calibration;    Training;    99 General And Miscellaneous//Mathematics, Computing, And Information Science;    Quality Assurance;   

DOI  :  10.2172/896187
RP-ID  :  DOE/EH/01002-1
RP-ID  :  FC02-01EH01002
RP-ID  :  896187

美国|英语

来源: UNT Digital Library

【 摘 要 】

Our goal (see Project Objectives) is to deliver a dosimetry system which will enable both a Pu body burden of 0.3 kBq, and a 30 cGy {gamma} ray dose, to be separately estimated with a confidence limit of {+-}30%. In terms of the numbers analyzed and the data we have accrued, we have direct quantitative evidence that we are on track to providing such a comprehensive independent dosimetry system for Mayak workers. We had previously demonstrated that intra-chromosomal aberrations measured in peripheral blood lymphocytes can be used as a sensitive long-lived low-background quantitative biomarker of densely-ionizing radiation dose in individuals exposed many years ago. We propose to calibrate the system such that it can be used to estimate both the densely-ionizing internal plutonium exposure and the sparsely-ionizing external exposure in Mayak workers exposed to different combinations of these over a prolonged period, mostly many years ago. Our objective is to deliver a dosimetry system (set of calibration parameters) which will enable both a comparatively low Pu body burden of 0.3 kBq, and a comparatively low 30 cGy {gamma} ray dose (one of these or both of these) to be estimated with a confidence limit of {+-}30% (higher doses will of course be estimated with smaller confidence intervals and still lower doses with larger confidence intervals). (1) Draw blood, make metaphase slides and measure numbers of intra- and inter-chromosome aberrations (using the mBAND and mFISH techniques) in - (A) 255 healthy former Mayak workers who were exposed various combinations of internal and external exposures. The individuals were chosen from the data base of healthy former workers through computer simulation to optimize estimates of the dosimetry parameters. The individuals have both internal and external dose estimates from the SUBI Doses-99 system. (B) 85 healthy non-exposed controls with ages, gender, and smoking status, chosen based on computer simulation to optimize estimates of the dosimetry calibration parameters. (2) To assess the time course of loss of aberrations with age, measure intra- and inter-chromosomal aberrations in archival slides from 5 live healthy individuals from whom blood has been repeatedly drawn over periods of more than 20 years. (3) Analyze the above results using appropriate regression techniques to provide a deliverable dosimetry system in which a measurement of intra and inter chromosomal aberrations in a blood sample taken from a previously exposed individual will yield separate estimates of both the internal and the external dose. (4) Training: Significant effort will be dedicated to training our SUBI colleagues in the use of the systems we have developed. (5) Quality Assurance: QA is central to this project. (6) Investigate variants of the current methodology to further enhance the practicality and ease of use of the dosimetry system.