Radiation Marks Chromosomes: Plutonium leaves genetic fingerprint

By examining specific types of long-lasting genetic rearrangements in blood cells, researchers have found a way to measure a person’s past exposure to plutonium radiation. Biophysicist David J. Brenner of Columbia University, who helped develop the new technique, says it could reveal health effects of radiation from radon and other sources.

RADIANT COLORS. In an example of intrachromosomal aberration, a normal portion of the chromosome (between red arrows, left) is missing from the chromosome at right. M.P. Hande, et al.

Radiation comes in two broad classes. Densely ionizing radiation from plutonium and radon burrows microscopic tunnels through living tissues and knocks things out of kilter along these tracks. Sparsely ionizing radiation from gamma rays and X rays distributes its effects more diffusely, like the pattern from a shotgun rather than a rifle.

The difficulty of quantifying past exposures to these two classes of radiation has been a stumbling block for researchers working to assess health risks associated with radiation.

In search of a biological marker for densely ionizing radiation, Brenner and his colleagues in Russia and Singapore focused on genetic irregularities known as stable intrachromosomal aberrations. These anomalies, which can persist for years without harming the cell, form when a single chromosome suffers multiple breaks and, while repairing itself, reverses or loses a piece of DNA.

The researchers studied chromosomes taken from blood cells of 26 former workers at the Mayak nuclear plant in Russia. Some had received large doses of densely ionizing radiation while processing plutonium. Others, who had maintained the reactor, faced sparsely ionizing radiation from gamma rays.

Brenner’s team applied dyes known as fluorochromes to a single pair of matched chromosomes from each of more than 100 cells from each volunteer. The dyes adhere to specific regions of the chromosome to produce a distinct pattern of painted bands. When their computer identified a chromosome with an unusual banding pattern, the researchers chalked up an intrachromosomal aberration.

The researchers also used a related method in which each chromosome in the normal genome is dyed a different color. Then they could identify abnormalities in which DNA had been exchanged between, rather than within, chromosomes.

Mayak workers highly exposed to plutonium had 55 times as many stable intrachromosomal aberrations as their reactor-based counterparts had, Brenner’s team reports in the May American Journal of Human Genetics. Individuals in the two groups showed similar numbers of abnormalities resulting from swaps between chromosomes. Because past research has suggested that the groups had similar total exposures to radiation, these results suggest that stable intrachromosomal aberrations primarily reflect densely ionizing radiation, Brenner says.

The new study is the first to show a biological fingerprint specific to that form of radiation in people, says Michael Cornforth of the University of Texas in Galveston. Such a marker might distinguish between the health effects of densely and sparsely ionizing radiation in victims of atomic bombs, he says.

Applying the new technique to research on radon gas may be a challenge, cautions epidemiologist Jonathan M. Samet of Johns Hopkins University in Baltimore. Because plutonium chemically mimics calcium, the body incorporates it into bones, where it can irradiate immature blood cells in the marrow at close range, he says. Radon, which is typically inhaled and expelled without being absorbed, primarily affects lung tissues and may therefore leave a different fingerprint on blood cells.

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