NASA - National Aeronautics and Space Administration

OpNom:

Overview | Description | Applications | Operations | Results | Publications | Imagery

Experiment Overview


Information provided courtesy of the Erasmus Experiment Archive.
Brief Summary

Chromosomal Aberrations in Blood Lymphocytes of Astronauts-1 (Chromosome-1) studies space radiation on humans. The expected results will provide a better knowledge of the genetic risk of astronauts in space and can help to optimize radiation shielding.

Principal Investigator(s)

Günter Obe, Ph.D., University of Duisburg, Essen, Essen, Germany

Co-Investigator(s)/Collaborator(s)

Christian Johannes, Ph.D., University of Duisburg, Essen, Essen, Germany

Markus Horstmann, Ph.D., University of Duisburg, Essen, Essen, Germany

Wolfgang Goedecke, Ph.D., University of Duisburg, Essen, Essen, Germany

Developer(s)

Johnson Space Center, Human Research Program, Houston, TX, United States

Sponsoring Space Agency

European Space Agency (ESA)

Sponsoring Organization

Information Pending

Research Benefits

Information Pending

ISS Expedition Duration:

December 2001 - October 2005

Expeditions Assigned

4,7,8,10,11

Previous ISS Missions

An earlier version of this experiment flew on the Space Shuttle and the Russian Space Station Mir. This investigation has been performed on ISS Expeditions 6-11.

^ back to top

---

Experiment Description

Research Overview

• This study will assess changes in the morphology of chromosomes, particularly chromosomal aberrations. The frequency and the type of chromosomal aberrations depend on characteristics and doses of ionizing radiation the crewmembers are exposed to while in orbit.



• Chromosomes collected from blood lymphocytes are scored for different types of abnormalities before and after a stay on ISS. Some of the analysis methods are new, and will provide a new way of visualizing all changes, particularly those increasing the risk of cancer.

Description

Crewmembers are exposed to radiation when they leave the protection of Earth's atmosphere. Ionizing radiation in particular can damage chromosomes, causing mutations such as chromosome aberrations. To assess the genetic impact of this radiation, blood is drawn before and immediately after flight by venous puncture. The blood is then cultured and the lymphocytes are stimulated to undergo mitosis (the process of cell division). In the first mitosis, at about 48 hours of incubation, the process is stopped and the chromosomes are prepared and stained using three different methods of microscopic analysis to assess all types of aberrations induced by ionizing radiations. These methods are:

• Classic Giesma staining, which allows the researcher to investigate changes in the morphology of the chromosomes. Chromosomes have a natural x-shape. Structural changes detected using Giesma include dicentric (the two chromatids of each chromosome are attached twice) and ring chromosomes or fragments (chromosome pieces without a centromere).



• Multicolor Fluorescence In-Situ Hybridization (mFISH), which scores reciprocal translocations and insertions (exchange of parts between different chromosomes).



• Multicolor Banding Fluorescence In-Situ Hybridization (mBAND) of the selected chromosome pair 5, which scores for inversions and translocations between homologous chromosomes (exchange or relocation of deoxyribonucleic acid (DNA) parts within the same chromosome pair).

A quantitative comparison between preflight and postflight aberration values will give information about the chromosome-breaking effects of cosmic radiation in blood lymphocytes of space travelers. Information will be generated concerning the participation of each chromosome pair in aberration formation as well as the interchromosomal and intrachromosomal distribution of different aberration types. The association of chromosomal aberrations with an enhanced cancer risk stresses the importance of the planned research.

^ back to top

---

Applications

Space Applications

From this study scientists may be able to better assess risk factors for genetic damage in space and help develop new methods for protecting crewmembers. Understanding and reducing the risk of radiation is important for safe long duration travel in space, including stays on the Moon and travel to Mars.

Earth Applications

The knowledge gained from this investigation will give scientist's insight into the exact chromosome from which particular mutations arise.

^ back to top

---

Operations

Operational Requirements

Chromosome-1 does not have any inflight requirements. Samples will be taken before and after flight.

Operational Protocols

The researchers will take venous blood samples (10 to 15 ml from the crew participants shortly before and after flight.

^ back to top

---

Results/More Information

According to NASA estimates, the uncertainties in radiation risk assessment for deep-space mission are unacceptably high. By far, the greatest fraction of such uncertainty is from our poor knowledge of human biological response to space radiation. Durante et al. (2003) conducted a long-term study in which chromosomal changes in peripheral blood lymphocytes from 33 cosmonauts involved in both long and short-duration space missions on Mir and the ISS were measured over a period of 11 years. Changes in blood lymphocyte chromosomes are the most widely used indicators of radiation exposure, and a direct comparison of risk estimates with biological measurements is possible because chromosomal alterations in peripheral blood lymphocytes have been validated as biomarkers of cancer risk (Durante, 2005).

So far, research results showed the only significant change was in one type of chromosomal damage known as dicentrics (2 partial chromosomes joined at broken ends resulting in a chromosomal structure having 2 distinct pinched areas called centromeres) in the pooled lymphocyte sample from 15 crewmembers returning from their first long-term flight. The number of these postflight dicentrics decline with time after the first space flight as expected due to cell turnover, but also it appears that subsequent long-term missions lead to less chromosomal alterations than the first flight. It is also reported that the frequency of complex-type exchanges between chromosomes for postflight was very low for astronauts involved in space missions lasting from 2 to 6 months in low Earth orbit (Durante et al. 2004). Other studies, focusing on chromosome 1, 2, and 5 in the lymphocytes of astronauts, did not detect any changes or find correlation between space flight duration, the number of flights, and extra-vehicular activity (EVA) duration with chromosome damage. These results scrutinize the concept that radiation effects in space are simply additive, and further study is needed to determine the true mechanism for this adaptation (Horstmann et al., 2005; Greco et al., 2003).

Scientists will be able to better assess risk factors for genetic damage from space exposure from these findings, and the large uncertainties can be reduced by improving our basic understanding of the underlying biological processes and their disruption caused by space radiation. It is unlikely that the radiation risk problem for space exploration will be solved by a simple countermeasure, such as spacecraft shielding or protective drugs against ionizing radiation. Rather, the risk will be understood and controlled through more basic research in the field of cancer induction by charged particles (Durante and Cucinotta, 2006).

^ back to top

---

Results Publications

George KA, Rhone J, Chappell LJ, Cucinotta FA.  Cytogenetic biodosimetry using the blood lymphocytes of astronauts. Acta Astronautica. 2012 May; epub. DOI: 10.1016/j.actaastro.2012.05.001.


Durante M, Ando K, Furusawa Y, Cucinotta FA, Obe G, George KA.  Complex chromosomal rearrangements induced in vivo by heavy ions. Cytogenetic and Genome Research. 2004; 104: 240-244. DOI: 10.1159/000077497.


Horstmann M, Durante M, Johannes C, Pieper R, Obe G.  Space radiation does not induce a significant increase of intrachromosomal exchanges in astronaut lymphocytes. Radiation and Environmental Biophysics. 2005; 44: 219-224. DOI: 10.1007/s00411-005-0017-0.


Durante M, Greco O, Gialanella G, Grossi G, Pugliese M, Scampoli P, Snigiryova GP, Obe G.  Biological dosimetry in Russian and Italian astronauts. Advances in Space Research. 2003; 31(6): 1495-1503. DOI: 10.1016/S0273-1177(03)00087-5.


Durante M, Snigiryova GP, Akaeva E, Bogomazova A, Druzhinin S, Fedorenko BS, Greco O, Novitskaya NN, Rubanovich A, Shevchenko V, von Recklinghausen U, Obe G.  Chromosome abberation dosimetry in cosmonauts after single or multiple space flights. Cytogenetic and Genome Research. 2003; 103: 40-46. DOI: 10.1159/000076288.


Durante M.  Biomarkers of Space Radiation Risk. Radiation Research. 2005; 164(4 Pt 2): 467-473. PMID: 16187751.

^ back to top

---

Ground Based Results Publications

^ back to top

---

ISS Patents

^ back to top

---

Related Publications

Durante M, Horstmann M, Obe G.  Distribution of breakpoints and fragment sizes in human chromosome 5 after heavy-ion bombardment. International Journal of Radiation Biology. 2004; 80(6): 437-443.


Obe G, Reitz G, Facius R, Johannes I, Johannes C.  Manned missions to Mars and chromosome damage. International Journal of Radiation Biology. 1999; 75(4): 429-433. PMID: 10331847.


Durante M, Johannes C, Horstmann M, Chudoba I, Obe G.  Chromosome intrachanges and interchanges detected by multicolor banding in lymphocytes: searching for clastogen signatures in the human genome. Radiation Research. 2004; 161: 540-548.


Durante M, Horstmann M, Johannes C, Obe G.  Chromosomal intrachanges induced by swift iron ions. Advances in Space Research. 2005; 35(2): 276-279. DOI: 10.1016/j.asr.2004.12.031.


George KA, Wu H, Willingham V, Cucinotta FA.  The effect of space radiation on the induction of chromosome damage. Physica Medica: European Journal of Medical Physics. 2001; 17(Suppl 1): 222-225. PMID: 11776981.


Obe G, Johannes I, Johannes C, Reitz G, Hallman K, Facius R.  Chromosomal aberrations in blood lymphocytes of astronauts after long-term space flights. International Journal of Radiation Biology. 1997; 72(6): 727-734.


Wu H, George KA, Willingham V, Cucinotta FA.  Comparison of chromosome aberration frequencies in pre- and post-flight astronaut lymphocytes irradiated in vitro with gamma rays. Physica Medica: European Journal of Medical Physics. 2001; 17(Suppl 1): 229-231. PMID: 11776983.


Goedecke W, Obe G, Bergau L.  Cytogenetic investigations in flight personnel. Radiation Protection Dosimetry. 1999; 86(4): 275-278. PMID: 11543396.


Fedorenko BS, Druzhinin S, Yudaeva L, Akatov YA, Snigiryova GP, Novitskaya NN, Shevchenko V, Rubanovich A, Petrov VP.  Cytogenetic studies of blood lymphocytes from cosmonauts after long-term space flights on Mir station. Advances in Space Research. 2001; 27(2): 355-359. PMID: 11642297.

^ back to top

---

Related Websites

International Space Station Medical Project (ISSMP)

Department of Genetics and Cytogenetics, University of Essen

^ back to top

---

Imagery

Giemsa stained metaphase with a chromatid break (one of the arms of the chromosome broke off). Image on the right is a detailed of the chromatid break. It is also visible in the image on the left, in the lower right corner of the picture. Image courtesy of NASA.
+ View Larger Image


Giemsa stained metaphase with several aberrations, i.e. polycentric chromosomes and acentric fragments. Polycentric chromosomes are attached to each other multiple times (unaltered chromosomes have one center). Acentric fragments have no attachment to the rest of the chromosome they originate from. Image courtesy of NASA.
+ View Larger Image


Researchers use mFISH to study human chromosomal pairs. Multi-color fluorescence in situ hybridization (mFISH) metaphase with an interstitial deletion of chromosome 1. The Chromosome 1 pair are the long yellow chromosomes located in the right center of the (that is the chromosome with the deletion) and on the left outer center of the picture. Image courtesy of University of Duisburg-Essen.
+ View Larger Image


Researchers use mFISH to study human chromosomal pairs. Multi-color fluorescence in situ hybridization (mFISH) metaphase with an interstitial deletion of chromosome 1. Chromosomes organized according to their pair number. Image courtesy of University of Duisburg-Essen.
+ View Larger Image


Multi-color fluorescence in situ hybridization (mFISH) metaphase with a reciprocal translocation between chromosomes 3 and 7. Image courtesy of University of Duisburg-Essen.
+ View Larger Image


Multi-color fluorescence in situ hybridization (mFISH) metaphase with a reciprocal translocation between chromosomes 3 and 7. Chromosomes organized according to their pair number. Image courtesy of University of Duisburg-Essen.
+ View Larger Image


Multi-color banding fluorescence in situ hybridization (mBAND) is done on Chromosome 5 only. This image depicts a chromosome 5 with an interstitial deletion (part of the chromosome is detached). Image courtesy of University of Duisburg-Essen.
+ View Larger Image


Multi-color fluorescence in situ hybridization (mFISH) metaphase with a complex translocation pattern. Translocations are present between chromosome 3 and the X-chromosome; chromosomes 7 and 21, and chromosomes 7, 12 and 15.Image courtesy of University of Duisburg-Essen.
+ View Larger Image


Multi-color fluorescence in situ hybridization (mFISH) metaphase with a reciprocal translocation between chromosomes 9 and 11 (encircled). Image courtesy of University of Duisburg-Essen.
+ View Larger Image