Answer to Question #13187 Submitted to "Ask the Experts"

I am having trouble understanding indirect ionization and its effects on the DNA. Could you please clarify?

 

I should note up front that the term "indirect" as it applies to radiation effects has two important aspects to its definition; I cannot discern definitively which concern is yours, so I will attempt to discuss both.

The first aspect relates to the use of "indirect" in reference to indirectly ionizing radiations. These are radiations that carry no electrical charge and produce ionization by first setting free a charged particle, which itself may then traverse material producing further ionization events along its path until it has lost essentially all its kinetic energy. The only indirectly ionizing radiations of practical concern are (1) gamma rays and x-rays (ionizing photons), both of which are electromagnetic radiations (similar to light but of much higher energy) and (2) neutrons, which often interact with the nuclei of atoms, sometimes setting free a proton, which may expend its energy as it travels along causing further ionization of atoms or molecules along its path. You can find more description of these processes in the answer of question number 9434 on the Ask the Experts website. The electrons and protons set free by photons and neutrons, respectively, are charged particles, and they are referred to as directly ionizing radiation.

These directly ionizing charged particles produce a large number of ionization events per unit path length traversed in material such as tissue, including individual cells and the genetic material, DNA, contained within the cell nuclei. As you are likely aware, the DNA strands are very long chains of nucleotides, which are made of sugar molecules associated with phosphate groups, that are paired together by particular organic bases that bind to the chains and couple together through hydrogen bonds (rather weak electrostatic bonds between hydrogen, carrying some net positive charge, and a more electronegative part of another molecule). When one or more of these ionizing events takes place in, or very close to, a DNA molecule it may result in energy transfer that may, for example, rupture a chemical bond in a strand of DNA that could possibly result in some deleterious effect(s). The body does have protection and repair mechanisms that are quite effective, and such DNA breaks are often repaired when the breaks are reconnected through biochemical mechanisms. Sometimes multiple ionization events may result in breakage of both DNA strands in a molecule. Such breaks are more difficult for the body to repair and could eventually lead to deleterious effects. The protons set free by some neutron interactions are much more densely ionizing than are the electrons from photon interactions with the result that if such protons pass near a DNA molecule they are more likely to produce double strand breaks than are electrons set free by photons, the electrons producing many fewer ionizations per unit path length traversed.

The second aspect as regards the term "indirect" refers to biological effects that are not induced directly by the ionizing event (e.g., energy transferred to a chemical bond, leading to its breakage) but rather by the interactions of certain chemical species that are produced by radiation interactions in materials of the body. Thus, the radiation, which may be either directly or indirectly ionizing, may interact with water in the body, and some of these reactions will result in the production of chemical species referred to as free radicals. These are chemical entities that carry one unpaired electron, a characteristic that makes them very reactive from a chemistry standpoint. They may interact directly with biological molecules, including DNA, or they may react to produce additional chemical oxidizing species. An example of a common free radical that one would expect from irradiation of water in the body would be the hydroxy free radical, symbolized OH, a very reactive species that could directly result in a bond rupture in a DNA strand. It is also possible for two hydroxy radicals, produced very close together, to chemically combine, each sharing its free electron with the other to yield a molecule of hydrogen peroxide, H₂O₂, a rather strong chemical oxidizing agent that could also go on to damage DNA or other molecules.

I realize that we have covered quite a bit. I hope this discussion is not overly confusing and that it gives you some insight to help resolve your concerns. Among all the toxic agents that we are exposed to, ionizing radiation is probably the most highly studied. We have learned a great deal about its interactions and effects, but there are still things that we need to learn. I am pleased to hear that you are undertaking some study of this bio-effective agent to acquaint yourself with some of what we do know. Best wishes in your continuing studies.

George Chabot, PhD