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University of Essen FB9 Department of Genetics Universitätsstr. 5 D-45117 Essen (Germany). Chromosomal Aberrations in Blood Lymphocytes of Astronauts Principal Investigator: Prof. Dr. Günter Obe Co-Investigators: Markus Horstmann Dr. Christian Johannes.

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University of Essen FB9 Department of Genetics Universitätsstr. 5 D-45117 Essen (Germany)

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University of essen fb9 department of genetics universit tsstr 5 d 45117 essen germany

University of EssenFB9 Department of GeneticsUniversitätsstr. 5D-45117 Essen (Germany)

Chromosomal Aberrations in Blood Lymphocytes of Astronauts

Principal Investigator: Prof. Dr. Günter Obe

Co-Investigators: Markus Horstmann

Dr. Christian Johannes


Scientific background

The genetic material is mainly situated in chromosomes

Scientific Background

Body cells contain 2x23 chromosomes (2n=46)

Cultured lymphocytes undergo mitosis which allows to prepare chromosomes and analyze them with the light microscope

Changes in the morphology of chromosomes (chromosomal aberrations, chromosome mutations) can be recognized and quantified


Scientific background1

Scientific Background

DNA is damaged by ionizing radiation, which

may lead to chromosomal aberrations

Chromosomal aberrations may lead to an elevated risk of cancer

Frequencies of chromosomal aberrations depend on characteristics and doses of ionizing radiation


University of essen fb9 department of genetics universit tsstr 5 d 45117 essen germany

Lesions in chromosomal DNA following treatment with mutagenic carcinogens(From G . Obe and A.T. Natarajan, 1982)


Radiation induced dna damage

Radiation induced DNA damage

gamma-, beta-, X-rays (low LET) alpha-, neutron rays (high LET)

Dose effect relationships for dicentrics and translocations following exposure to low or high LET radiation

(From G. Obe and A. T. Natarajan, 1999)


Metaphase preparation from human lymphocytes giemsa staining

Metaphase preparation from human lymphocytes(Giemsa staining)

a: Undamaged metaphaseb: Radiation induced dicentric

chromosome (left) with fragment (top right)


Multiaberrant cell

Multiaberrant Cell

(Giemsa staining)

Arrowheads indicate

centromeres in poly-

centric chromosomes


Human metaphase chromosomes painted with the mfish method

Human metaphase chromosomes “painted” with the mFISH method

Reciprocal exchange

(translocation between chromosomes 11 and 12)


Chromosome 5 painted with the mband method

Chromosome 5 „painted“ with the mBAND method

The right chromosome shows a large inversion of its middle part whose breakpoints are indicated by dotted lines.

(White dots = centromeres)


Scientific background2

Chromosomal aberrations in peripheral blood lymphocytes of astronauts

indicate an elevated mutagenic and carcinogenic risk due to radiation in space

Scientific Background

Result


University of essen fb9 department of genetics universit tsstr 5 d 45117 essen germany

Dicentric chromosomes in lymphocytes of seven MIR cosmonauts (C1-C7) before and after their last space flight (120-198 days). (Data from: Obe et al, 1997)

The frequencies of

dicentrics can be

calculated by taking

radiobiological parameters

such as half-life of

lymphocytes and

dose-effect characteritics

into account.


Conclusions

The analysis of chromosomal aberrations in lymphocytes of astronauts allows to answer the following questions:

1. Is exposure to space radiation associated with mutagenic and carcinogenic risks ?

2. What radiation protection measures have to be taken to minimize risks of exposures to space radiation ?

Conclusions


Experiment design

To assess the genetic impact of ionizing radiations, blood (10-15 ml) is drawn before and shortly after flights by venous puncture

Blood cultures will be set up in our laboratory, using standard procedures

Chromosomes will be stained using procedures to assess all types of aberrations:

(1) Classical Giemsa staining

(2) Multi-color fluorescence in situ hybridization (mFISH)

(3) Multi-color banding fluorescence in situ hybridization (mBAND)

of chromosome 5

Experiment Design


Medical risks

Venipuncture performed by a physician is nearly free of any risk.

Minor temporary discomfort or pain.

Hematoma associated with extravasation of blood during or following venipuncture.

Infection or thrombophlebitis resulting from venipuncture. This is infrequent in healthy persons.

The following safety precautions will be taken to mitigate any risk associated with venipuncture:

Procedure will be performed by experienced personnel.

Use of standard aseptic techniques.

Use of sterile disposable hardware.

Possible Inconveniences or Discomforts

No additional inconveniences or discomforts have been identified.

Medical Risks


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