[New Science article below]
M. Prakash Hande,1,* Tamara V. Azizova,2 Charles R. Geard,1 Ludmilla E. Burak,2 Catherine R. Mitchell,1 Valentin F. Khokhryakov,2 Evgeny K. Vasilenko,3 and David J. Brenner1
1Center for Radiological Research, Columbia University, New York; and 2Southern Urals Biophysics Institute and 3Mayak Production Association, Ozyorsk, Russia
Received December 18, 2002; accepted for publication February 10, 2003; electronically published April 4, 2003.
Speculation has long surrounded the question of whether past exposure to ionizing radiation leaves a unique permanent signature in the genome. Intrachromosomal rearrangements or deletions are produced much more efficiently by densely ionizing radiation than by chemical mutagens, x-rays, or endogenous aging processes. Until recently, such stable intrachromosomal aberrations have been very hard to detect, but a new chromosome band painting technique has made their detection practical. We report the detection and quantification of stable intrachromosomal aberrations in lymphocytes of healthy former nuclear-weapons workers who were exposed to plutonium many years ago. Even many years after occupational exposure, more than half the blood cells of the healthy plutonium workers contain large (>6 Mb) intrachromosomal rearrangements. The yield of these aberrations was highly correlated with plutonium dose to the bone marrow. The control groups contained very few such intrachromosomal aberrations. Quantification of this large-scale chromosomal damage in human populations exposed many years earlier will lead to new insights into the mechanisms and risks of cytogenetic damage.
* Present affiliation: Department of Physiology, National University of Singapore, Singapore.
source: http://www.journals.uchicago.edu/AJHG/journal/issues/v72n5/024812/brief/024812.abstract.html 28may03
How much damage does cosmic radiation do to frequent flyers? Is depleted uranium from shells causing cancers in former war zones such as Kosovo and Iraq? The discovery that certain kinds of radiation leave a distinctive pattern of damage in our cells could help answer these questions.
"If this works, we'll be able to take a measurement and see the lifetime exposure in that person," says David Brenner of Columbia University in New York. "Often there is no other reliable record of individual exposure." It is this uncertainty about radiation exposure that makes it hard to pin down the health risks.
"That they found this effect was there at all is significant," says Michael Cornforth, a radiation biologist at the University of Texas Medical Branch in Galveston. "But I was flabbergasted by how clear-cut it was."
Radiation is harmful because of its ionising effect, which can break DNA chains. If the broken pieces are rejoined incorrectly, the resulting genetic scrambling can harm cells or, far worse, set them on the road to cancer.
Some genetic damage is easy to spot, such as when parts of different chromosomes are exchanged - known as interchromosomal changes. But because mutagenic chemicals can also cause such exchanges, this is not a reliable indicator of exposure to radiation.
Heavy particles
Researchers have long suspected that slow-moving, heavy particles such as alpha particles and neutrons should leave a characteristic pattern of damage. These kinds of radiation are known as "densely ionising" because they wreak havoc within a short tunnel; "sparsely ionising" X-rays or gamma rays spread their damage along a much longer path.
Because the damage from densely ionising radiation is so concentrated, it is far more likely to hit one chromosome several times, triggering deletions or reordering of its DNA.
Testing for radiation exposure
Detecting intrachromosomal changes like these has been extremely difficult till now. But Brenner's team, together with a Russian group, took advantage of new dyes to "paint" bands on chromosomes. Image analysis software translates this into false-colour pictures (see graphic), making it easy to spot any rearrangements.
The team used the technique to analyse chromosome 5 in thousands of blood cells from 31 people who had worked at a secret nuclear weapons facility near Ozyorsk in Russia. Though most of the workers were last exposed to densely ionising radiation from plutonium over 10 years ago, the team found a surprising amount of damage.
Nearly four per cent of blood cells in highly exposed workers had rearrangements within chromosome 5. Extrapolating from this, Brenner thinks that 62 per cent of these workers' blood cells have damage within at least one chromosome.
Workers with moderate levels of exposure had a lower level of damage, while those with no radiation exposure had none. Even workers at a nuclear reactor exposed to high levels of sparsely ionising gamma rays and mutating chemicals had very few intrachromosomal changes, though they had significant interchromosomal damage.
There is still a lot of work to do before the technique can be widely adopted. "We need to automate the technique," Brenner says. "Even in this small study, it took us two years to look at all the cells."
Journal reference: The American Journal of Human Genetics (vol 72, p 1162)
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