Dr. David J. Brenner
Center for Radiological Research, Columbia University
630 West 168th St
New York, NY 10032
Phone: 212-305-9930
Fax: 212-305-3229
E-mail: djb3@columbia.edu
Number of Human Subjects projects reported: 1
| CU-00-POC | "A validated high-LET radiation specific biomarker in the Mayak worker cohort" |
"A validated high-LET radiation specific biomarker in the Mayak worker cohort"
Principal Investigator: Dr. David J. Brenner, Columbia University
Project started in: 2000
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: FIB-1 Mayak
Most recent approval: 03/05/02
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 24
Reporting period for number of human subjects:
Fiscal Year 2002
Type(s) of Human Subjects Involvement:
a) OBJECTIVES
The overall goal of this work is to test the hypothesis that a specific chromosomal biomarker exists and is detectable for past exposure to high-LET radiation such as a plutonium alpha particles, even in the presence of other mutagens or clastogens, such as tobacco, organic chemicals, or gamma rays. Such a biomarker would significantly increase the power of epidemiological studies of individuals exposed to densely-ionizing radiations such as alpha particles (e.g., radon, Pu workers) or neutrons (e.g., DOE/NRC workers, airline personnel).
The proposed biomarker is the ratio of induced intra-arm to inter-chromosomal aberrations - the H value. Both theoretical and experimental studies have suggested that this ratio will be different by a factor of about 3 between low and high LET. Because both types of aberrations (intra-arm and inter-chromosomal aberrations) are 1) frequent and 2) measurable at long times after exposure, the H ratio appears to be a practical biomarker of high-LET exposure.
The hypotheses under test are
i)that this H value will be significantly and detectably different for alpha particles compared to that produced by chemical carcinogens / clastogens, such as tobacco or hydrocarbons, and also different from that produced by x- or gamma- rays.
ii)that an intermediate-dose in-vivo plutonium exposure can be reliably identified and reconstructed with adequate statistical power, even if the subject had also received significant exposure to chemical carcinogens/clastogens or gamma rays. This would be done using fluorescent in-situ hybridization (FISH) technology to measure the H value. Appropriate probes for intra-arm aberrations have been developed, and probes for inter-chromosomal aberrations are readily available.
b. METHODOLOGY
To make FISH-based H-value measurements on peripheral blood lymphocytes from individuals in the Mayak worker cohort who were exposed to a wide range of plutonium exposures and gamma ray exposures. The blood work and chromosome preparations (slides) are being done under a different grant to Mayak scientists. At Columbia, we analyze the metaphase preparations. The large number of individuals involved, together with the broad spectrum of exposures, means that this cohort offers a unique opportunity to test the hypotheses about the H value.
In the current (Phase I) component, we are establishing co-operative relationships, accessing the Mayak worker registries, and establishing protocols including QA/QC. In addition, to assess feasibility, we are assessing H values on 25 individuals, whose blood was obtained and processed by Mayak scientists, under the auspices of their grant.
IONIZING RADIATION
c. None
INVOLVEMENT OF HUMAN SUBJECTS
PROCEDURES INVOLVING HUMAN SUBJECTS
d1.The required volume of peripheral blood is collected aseptically in a sodium heparinised vacutainer tube or syringe.
RISKS
d2. The hazard for this procedure is minimal; a faint soreness or bruise in the area of the needle puncture may occur.
PRIVACY/CONSENT
d3:No personal identifiers are linked to the blood samples, only details of the past exposure to radiation, as well as age, gender, and smoking history.
The informed consent form follows:
Branch No. I of the Institute of Biophysics with the support of the U.S. Department of Energy, and in collaboration with Columbia University, New York, USA, is collecting and storing blood from individuals who might have been exposed to ionizing radiation as a result of operations of Mayak Production Association. The blood sample will be processed at Branch No. I of the Institute of Biophysics and used in future biomedical studies aimed at a better understanding of radiation effects on health in exposed individuals. Scientists using up-to-date genetic and molecular techniques and equipment will conduct these studies. Application of these new technologies carries promise of future development of a better understanding of the effects of radiation on health in each individual.
We are inviting you to make a donation of blood and take part in this effort
If you agree to participate, you will fill in a questionnaire concerning your occupational and medical histories. The doctors-investigators will also review your medical records and analyze your occupational history. In addition, a blood sample will be collected from you. Your biological material will be a donation to help advanced science and you will not be compensated. A nurse will collect a blood sample from your vein. First of all your arm will be cleaned by alcohol to prevent infection. Blood sample will be derived from your vein by means of sterile needle into a special test-tube.
The hazard for you related to this procedure is minimal; a faint soreness or bruise in the area of the needle puncture may occur. All these procedures will be conducted by the attending nurse or physician and presents no hazard to you. All these procedures will be free of charge for you.
The benefit of studies to be performed is that you and similarly exposed individuals may acquire in the future more complete knowledge on the effects radiation may have on your health. On receiving results of future studies from your biological material and in the case of any abnormalities this information will be passed to your doctor for more thorough examination of you and conducting relevant therapeutic-prophylactic measures.
Your donation of blood is voluntary and you can terminate it at any time. All information collected will be used only for scientific purposes, and will be stored confidentially in accordance with established Russian law. Only the specialists collecting the blood will know your identity. The medical information accumulated on you will be stored as records and as computer files under your unique numerical identifier (without your name) and only investigators for these specific studies will have access to it. Nobody will get this information without your written permission. Your biological sample will be also preserved with the numeric identifier. It will be used solely for the studies within the framework mentioned above and under the control of principal investigators. The part of your biological sample under your numeric identifier might be transferred for analysis to leading research laboratories in the US and other countries, but your identity will not be provided.
If you have any questions regarding the procedure, please feel free to contact Dr. Tamara Azizova.
If you have any questions concerning your rights as a subject of studies, you can contact the Director of FIB-1 Dr. Sergei Anatoliy Romanov or Chairman of the Institution Review Board (IRB) Dr. Galina Grigorjcvna Rusinova.
If you agree to make a donation to this program please sign this letter named "The Informed Consent":
I was told of the benefits as well as of insignificant unpleasant sensations at collection of blood samples which may occur. I give my consent for participation in do it at no charge. I understand that part of this biological material may be sent to and analyzed at leading research institutions in the US and other countries. I understand that the results of examinations within these studies will not be entered into my medical records. I am aware of my right to refuse to participate in the study.
___________________________________________________________
Name of the donor
Signature,
Date
CERTIFICATION OF THE OFFICER CONDUCTING THE PROCEDURE OF INFORMED CONSENT:
I certify that the nature and the purpose of this research have been explained to the participant. She/he had the opportunity to discuss this in detail. I have answered all her/his questions and she/he has agreed to participate in this research work.
___________________________________________________________
Officer's signature
________________________________ _____________
Name of the officer
Date