EFFECTS OF RADIATION ON DNA AND CELLS

Now that you are a member of the cognoscenti for your knowledge of radiation doses, it is time to explore what radiation does to cells and to DNA. The relative

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damage depends on the kind of radiation because the density of ionizations varies greatly for a у ray compared to an a particle (Figure 7.5). A p particle or у ray has a low density of ionizations, so they may well pass through a strand of DNA and cause no damage whatsoever, but an a particle causes a lot of damage. In particular, the ionizations may cause breakage of molecular bonds that hold the strands of DNA together.

Radiation can cause ionizations in many molecules in a cell, but numerous experiments over the years have shown that it is the damage to DNA that causes the biological effects. Alpha particles mainly break both strands of the DNA in what is called a double strand break (DSB) (Figure 7.5). Beta particles and у rays, which are the main types of radiation from fission products in spent nuclear fuel (see Chapter 9), can cause a variety of types of damage to DNA. They can cause DSBs if the cluster of ionization occurs in just the right place. More commonly, they can break just a single strand of the DNA, forming a single strand break (SSB). In addition, they can cause various kinds of damage to the bases in DNA or can cause linkages to form between DNA and proteins.

Of all of these types of damage, the main one that causes problems is the for­mation of DSBs. DNA that is broken in this way forms what are sometimes called “sticky ends” and they can be stuck back together with special repair enzymes. But they don’t always get stuck back together properly. Sometimes a piece of DNA is just lost from the end of a chromosome, in what is called a terminal dele­tion. Sometimes two DSBs are formed, and a piece in the middle of a chromo­some can be deleted (an interstitial deletion) or inverted (an inversion). Pieces of DNA from different chromosomes can also get stuck together, forming what
is known as a reciprocal translocation, which is not lethal, or a dicentric (a chro­mosome with two centromeres), which is lethal to the cell. These various possi­bilities for sticking broken pieces of DNA back together form what are known as chromosomal aberrations, many of which are visible through a light microscope when you look at chromosomes in mitosis. Some of these chromosomal aber­rations are lethal to cells and some of them are benign, having no effects what­soever. And some of them may cause mutations that can cause a cell to become cancerous later (7).

So how much damage are we talking about? Now it is important to talk about a specific dose of radiation. A dose of 1 Gy of p or у radiation causes a rather large amount of damage in the DNA of a cell: about 20-40 DSBs, 1000 SSBs, 1,000 dam­aged bases, and 150 DNA-protein crosslinks (8, 9). The number of DSBs from the same dose of a particles is about three times as much as for у rays (9). Amazingly, the majority of cells that receive 1 Gy of у rays are not killed. How is that possible?

There are several factors that allow our cells to sustain so much damage from radiation without being killed. One factor is that we are diploid organisms—that is, we have two copies of our chromosomes—so damage to one copy can often be overcome by undamaged DNA on the other chromosome. Another factor is that the vast majority (about 98%) of our DNA does not code for anything. Genes contain coding DNA (exons) and long stretches of DNA known as introns that are spliced out before RNA and proteins are made, so much of the damage from radiation may be in regions of DNA that have no effect on the resulting proteins. There are also regions of DNA consisting of highly repetitive short sequences that do not code for anything. Finally, our cells have very sophisticated enzymatic repair machines that can fix most of the damage caused by DNA. This might be very surprising to you, and it apparently is unknown to Helen Caldicott and many anti-nuclear activists, who seem to believe that any radiation is going to cause cancer. In fact, the vast majority of damage to DNA caused by radiation is in DNA that has no apparent function or is repaired.