Ionizing Radiation and Genetic Mutations

Arjun Kumar
February 28, 2019

Submitted as coursework for PH241, Stanford University, Winter 2019

Introduction

Fig. 1: Ionizing radiation can induce frameshift mutations that disrupt the whole downstream protein sequence. (Source: Wikimedia Commons)

One of the most important factors in public fear vs. acceptance of nuclear energy is the fact that exposure to nuclear radiation is widely known to pose a significant risk to human health. Ionizing radiation, which includes X-ray, α, β, and γ radiation as well as charged atomic nuclei, is known to contribute to a variety of genetic diseases and cancers by causing genetic mutations. [1] This note examines the process by which ionizing radiation causes mutations, what sorts of mutations it can cause, and how this process leads to the diseases that dominate public perceptions of nuclear energy.

Genetic information and Mutations

The genetic information that defines humanity and determines what traits are passed down from parents to children is encoded in a large and complex molecule known as deoxyribonucleic acid (DNA). The DNA molecule is a polymer made up of repeating subunits forming a double helix structure, where each subunit is one of four possible nucleotides: adenine (A), cytosine (C), thymine (T), and guanine (G). The unique combinations of these DNA nucleotides are transcribed into ribonucleic acid (RNA) molecules; these RNA molecules are translated into one of 20 amino acid molecules, which together determine the structure and function of the proteins that perform countless functions in each human cell.

Ionization of DNA

Humans are exposed to radiation through common medical procedures such as X-rays and radioisotopes in diagnostic tests, as well as a background level of nuclear radiation from space, radioactive waste, nuclear testing, nuclear accidents, and a variety of other sources. [2] For most humans who aren't employed in high-exposure environments, this comes through low-dose (below 100 millisieverts) ionizing radiation, primarily in the form of Rn-22. [2]

The mechanism by which radiation ionizes atoms depends on whether it is particulate (e.g. α radiation, which is comprised of helium nuclei) or electromagnetic. Particulate radiation either directly ionizes or excites electrons in ways that are localized to the particular affected tissue. Photon radiation can transfer its energy via photoelectric interaction (where all its energy transfers into an electron and cause it to eject violently from the atom), Compton scattering (where part of the energy transfers into the electron and the remaining photon scatters elsewhere), or pair production (where the photon's energy is converted into matter, producing a positron and an electron). [2]

Using these various methods of energy transfer, ionizing radiation exerts effects on DNA molecules through direct action and indirect action. [2,3] In direct action, the radiation pushes an electron in the DNA molecule out of orbit, potentially disrupting the nucleotide at that location. [3] In indirect action (the more common source of radiation damage), the radiation ionizes water molecules and other molecules surrounding the DNA; this creates hydroxyl and alkoxy free radicals that have an unpaired electron, making them highly reactive and damaging to DNA. [2,3]

Downstream Effects

When one of the DNA nucleotide bases is disrupted, it creates downstream effects on the resulting RNA sequence, amino acid sequence, and protein structure and function. Mutations can include insertions or deletions of DNA bases, and in the case of frameshift mutations (depicted in Fig. 1), can disrupt the entire downstream amino acid sequence. The impact of mutations can be classified in several different ways: they can affect somatic (normal body) or germinal (sperm and egg) cells, at autosomal (22 non-sex chromosomes) or sex-linked (X or Y) chromosomes, affect genes in a dominant (guaranteed to be expressed) or recessive (may simply be a carrier) pattern, and exert major or minor effects on one or many genes. [4]

When these mutations happen in one of the many genes that regulate the rate of cell division (known as proto-oncogenes or tumor suppressor genes), it can lead to a variety of cancers. Survivors of radiation accidents and nuclear attacks have been shown to have a significantly elevated risk of cancers, largely due to increased probability from ionizing radiation of such mutations happening. [5] Interestingly, hereditary effects of these mutations have not been found in the children of Hiroshima and Nagasaki survivors, opening up new questions about whether this is due to a small sample size or how ionizing radiation may not exert the same effects on human sperm cells or egg cells. [5]

©Arjun Kumar. The author warrants that the work is the author's own and that Stanford University provided no input other than typesetting and referencing guidelines. The author grants permission to copy, distribute and display this work in unaltered form, with attribution to the author, for noncommercial purposes only. All other rights, including commercial rights, are reserved to the author.

References

[1] Health Effects of Exposure to Low Level of Ionizing Radiation (National Academies Press, 1990).

[2] O. Desouky, N. Ding, and G. Zhou, "Targeted and Non-Targeted Effects of Ionizing Radiation," J. Radiat. Res. Appl. Sci. 8, 247 (2015).

[3] R. R. Faden et al., "Final Report," Advisory Committee on Human Radiation Experiments, October 1995.

[4] E. L. Green et al., eds., Biology of the Laboratory Mouse, Second Edition (Dover, 1968).

[5] K. Kamiya et al., "Long-Term Effects of Radiation Exposure on Health," Lancet 386, 469 (2015).