DNA Mutation Caused by Ionizing Radiation

This is an article covering the Health Effects of Radiation in relation to the miracle of life. Within context it describes all ionizing radiation, but the greatest radiation threat comes from man-made radioactive pollution. These forms of radiation have the greatest potential to cause DNA mutation because they are extremely radioactive and can attack our cells at the closest levels. Please learn more about the terrible threat of man-made radioactive pollution by reading Heal and Protect: A Nuclear World.

The Miracle of Life

Life evolved in the presence of significant ionizing radiation from the Earth and Sky. Because of this, we are well adapted to the natural forms of radiation. The body has ways to mitigate this force of nature that is constantly trying to break apart and alter the molecules upon which life is built. It is constantly organizing and building, and ever engaged in an effortless struggle to counter the forces that would tear it apart and end the pulsating rhythm that is the miracle of life.

Every instant new cells are being formed so the body can grow, replace dead or damaged cells, repair tissues and perform a wide variety of body functions. Cells are formed by a process whereby one cell divides into two (mitosis). This is only possible because of DNA found in each cell. When one becomes two, the first step is to duplicate DNA because every cell has to contain the genetic information of the whole organism. DNA is the reason we exist and the most complex molecule in the known universe. Ionizing radiation is its great nemesis and yet the design of DNA and the body provide key advantages that allow them to prevail and sustain life as we know it.

The first advantage is the way the body shields the compact DNA, making it a difficult target to hit from outside the body. Most of our threat from background radiation is from outside of our body, so organisms that dwell on the surface of the Earth have the most sensitive tissues, like nervous system, heart, and brain behind skin and bone, which provide shielding. Cells that take the brunt of our environment, like skin and intestinal cells are constantly being shed and replaced. Alpha and beta radiation can’t even make it through the skin.

All tissues of the body are made up of cells. Inside of each cell is a small nucleus that contains the DNA. The nucleus of different cells can take on various sizes and shapes, but in general, it takes up a small volume of the cell. DNA takes up only 0.3% of this nucleus volume. Outstretched, a single DNA strand would be approximately six feet long, but in the nucleus, it is organized in tightly packed structures called chromosomes. Humans have 23 pairs of chromosomes in every cell nucleus of the body, representing nearly three billion base pairs and 21,000 known genes. Each chromosome is a very small target to hit.

The second, and key, advantage is the structure of DNA itself. Because DNA is organized as a double helix comprised of two identical strands with the same information, damage to one can be repaired with information from the second. This repair process is happening constantly in our bodies[1]. Every moment, DNA is repaired from damage caused by many different sources, such as radiation, toxins, or normal bodily processes, such as metabolism. This advantage is so key because it is not possible to prevent DNA damage, but the body has a back-up copy in every cell.

This is important because as we study how radiation can damage DNA, the most important criteria will become how damaged the DNA is. DNA that is severely damaged in multiple places along the strand or DNA that has both strands damaged is far less likely to repair correctly, and far more likely to parent cells with a DNA mutation.

The third advantage is the amazing functioning of the body which is constantly scavenging toxins, free-radicals, and killing cells that are damaged and not functioning properly. If a cell is significantly damaged, it can be terminated by a process of programmed cell death, called apoptosis. If a cell is stressed, for example, by radiation, heat, or viral infection, it can commit cell suicide, which limits the possibility of mutations that are carried forward by cell division. Severe exposures to radiation result in near immediate death because of massive cell death in the body. This highlights the importance of assessing the way radiation interacts with the cells.

How the body functions is still a frontier of science. We don’t understand all the nuances and ways that cells communicate or ‘decide’ what to do and how to do it. We are only beginning to unravel the complex functions and interactions of DNA and the rest of the amazing molecules that animate the cell.

We don’t understand all the effects of radiation on the body, especially radiation inside of the body. We’re learning, but the best we can do is use statistics based on studies to estimate the probability of health effects based on what we think exposures are. These studies tend to focus on the big effects, or the lagging indicators, like cancer and obvious birth defects, but they can miss more subtle and complicated contributions to disease. What we do know is that radiation can cause or contribute to nearly all diseases, especially cancer, and that no exposure to it can really be considered ‘safe.’

Health Effects of Radiation

Ionizing radiation damages living tissue. Because it has the energy to dislodge electrons from their orbits, it can break the bonds that hold molecules together. This results in damage, mutation, or death of the cells for all tissues in the body. Depending on the profile of radiation exposure (type, quantity, rate, and affected tissue), this can lead to a host of health complications including sickness, disease, cancer, and death. Of the many effects of radiation on the body, there are deterministic and stochastic effects to consider.

Deterministic Effects

Deterministic health effects occur reliably at higher exposures of radiation and are fairly well understood. At certain levels, harmful reactions in human tissues due to radiation are directly correlated to cell death and malfunction.

This results in radiation burns, acute radiation sickness (ARS), chronic radiation syndrome, or death. A recently removed nuclear fuel rod from a reactor will kill a person in seconds, no matter who they are, and certain levels of radiation will burn the skin and cause us to be sick.

Stochastic Effects

Stochastic health effects due to radiation, on the other hand, are unpredictable. They are perceived as random because of uncertainty regarding all the causal parameters and mechanisms behind them. It means there are effects, but they can’t be predicted precisely and need to be modeled using statistics. The same exposure may cause cancer in one and yet not in another. These stochastic effects include cancer, heritable mutations, abnormal physiological development (teratogenesis), cognitive decline, heart disease, diabetes, decreased immune function, aging[2], and other health disorders. Radiation can contribute to all these pathologies and yet because of the nuances of the person, the exposure, the conditions of the body, and other factors, it is not certain what the effect will be for each individual.

Heart disease, heart attack, premature aging, stroke, shortened lifespan, and cataracts have been shown to be induced by radiation exposure. Studies have shown significant increases in all these pathologies for the atomic bomb survivors and nuclear industry workers.

All our reproductive organs are attacked by radiation.  It is proven to cause birth defects, miscarriages, heritable mutations, and diseases affecting our children.

Radioactive elements can cross the placenta barrier and affect the unborn in utero. The fetus is much more sensitive to radiation than the adult. There are diseases that can take years to develop that are related to radiation exposure in utero, such as leukemia, muscular diseases, cancers, and heart issues. These effects we don’t fully understand because there are so many factors to grasp.

Mutation

When DNA is damaged, the result can be mutations that lead to cancers, heritable diseases, birth defects, and other serious health issues. The importance of DNA cannot be overstated. It is responsible for providing instructions on how to build and how to power every cell in our body.

DNA Damage Leads to Mutations

There are two types of DNA we are concerned with that are found in every cell of the body and both are susceptible to mutations. The first is intracellular DNA and it is the DNA most are familiar with.  It is found in the nucleus of each cell. This DNA is the very foundation of life responsible for cell replication, transmission of genetic information, and coding for all the blocks that build life. There is a single intracellular DNA molecule in each nucleus until the cell decides to divide and make a single copy to pass to its daughter cell.

The second is mitochondrial DNA (mtDNA). Mitochondria are found in every cell and are responsible for converting energy from food into a form that cells can use (adenosine triphosphate – ATP)[3]. They contain a very small amount of their own DNA responsible for coding 37 genes that provide instructions to make ATP and certain types of RNA. Tissues that use lots of energy have higher amounts of mitochondria, such as the heart muscle, but there are many copies of mtDNA in each cell, making them easier to damage by radiation.

Radiation damages DNA either directly, by colliding with it, or indirectly, by ionizing molecules and creating free-radicals that attack it. It can also damage DNA through another mechanism termed the ‘bystander effect’ (genomic instability) where an irradiated cell causes effects in a nearby, non-irradiated cell. If one cell is struck by radiation, the neighbor cells can also respond to this damage by exhibiting genetic changes or cell death[4] (1). This means that when only a portion of tissue cells are struck by radiation, the whole tissue is at risk for damage and cellular mutation. Studies have shown that irradiation of 10% of cells to alpha particle radiation results in the same amount of mutations as if all the cells were irradiated (2).

Ionizing Radiation is the Best at Damaging DNA in the Worst Ways

Combine the ‘bystander effect’ with direct and indirect damage to DNA, and this means that ionizing radiation is extremely efficient at damaging DNA, thereby killing or mutating cells. It is many times more potent at damaging DNA than other common chemical causes of DNA , such as hydrogen peroxide, common carcinogens, or UV-light[5] (3). It is more effective because it can cause double strand breaks (DSB) and locally multiply damage sites (LMDS) with ease. When both adjacent strands are broken, or damage is in multiple locations, then the DNA is likely not to be repaired correctly, leading to mutation.

Significant evidence points to the fact that double strand breaks are the primary cause of mutation and cancer[6] (4). This fact will be explored more as we look at external versus internal radiation exposures because internal radionuclides that irradiate the same cells continuously are more likely to cause double and multiple breaks.

DNA Mutation Leads to Disease and Cancer

Mutations in the intracellular and mitochondrial DNA both lead to health complications and cancer.

Mitochondrial DNA is particularly prone to somatic mutations and evidence links these mutations to primary human cancers, including breast, colon, stomach, liver, kidney, blood-forming tissue (leukemia), and immune cells (lymphoma)[7] (5).  There can be thousands of mitochondria in the more active tissues, such as the heart muscle. Each one is susceptible to radiation induced mutations.

Intracellular DNA that is damaged in germ cells (sperm or egg) can lead to mutations in our offspring — birth defects, diseases, disabilities, and other subtle abnormalities in body function. These heritable mutations can include cleft lip/palate, congenital heart defects, cystic fibrosis, muscular dystrophy, chromosomal diseases like Down syndrome, and chronic adult diseases such as coronary heart disease, hypertension, and diabetes.

Because DNA codes everything, DNA mutation can effect everything, from how we build cells to how we power them. Too often the studies on radiation focus on fatal cancers and obvious birth defects, but there is a wide range of health complications caused by radiation that may not be readily apparent when studying the risk models focused on cancer.

What We Don’t Know

Another frightening aspect to fully understanding DNA mutation and the risk that radiation poses is to understand the Nobel Prize winning studies conducted by Herman Joseph Muller on fruit flies. These studies showed that it can take up to twenty generations before genetic mutations manifest. This means that diseases like cystic fibrosis, diabetes, or any of the other six thousand known diseases that are genetically inherited, could take some time before they appear (6). Considering how much anthropogenic radiation has been released in such a short time in history, this is cause for significant concern.

None of the radiological protection standards take this into account, nor do scientists yet understand all the intricacies of genetic mutation, transmission of mutations, and how mutations can affect the health of our children.

In the executive summary of their latest report on the health effects of low-levels of radiation, the U.S. National Academy of Sciences committee on the Biological Effects of Ionizing Radiation (BEIR) identified clearly that additional research on “heritable genetic effects of radiation” was needed. They indicated there is uncertainty in how DNA breaks affected germ cells (reproductive cells) and how DNA mutation is associated with “multi-system development defects” in offspring (4).

End-notes:

[1] It has been estimated that between 10,000 and 40,000 DNA repair events happen every day from a variety of causes, most of them internal. This is small compared to the estimated 37 trillion cells in the human body (7).

[2] Free-radical damage, oxidative stress, mitochondrial damage, and DNA damage contribute to aging processes (8).

[3] All life has intracellular DNA in each cell. Plants don’t have mitochondrial DNA, but they have chloroplast DNA (ctDNA), which mostly codes for photosynthesis processes, performing the function of converting sun energy to food for the cell – the same essential function as our mtDNA.

[4] “Evidence accumulated over the past two decades has indicated that exposure of cell populations to ionizing radiation results in significant biological effects occurring in both the irradiated and non-irradiated cells in the population. This phenomenon, termed the ‘bystander response,’ has been shown to occur both in vitro and in vivo…genetic alterations, changes in gene expression and lethality occur in bystander cells that neighbor directly irradiated cells.”

[5] “It is the concentration of these damaged sites in local regions of the DNA (producing what we have called locally multiply damaged sites, LDMS) which is responsible for the effectiveness of ionizing radiation in inducing cell killing…It is clear that ionizing radiation (and bleomycin) are different from other agents in their ability to kill cells.”

[6] “..there is compelling evidence that the induction and interaction of DNA double-strand breaks is the principal mechanism for the production of chromosome aberrations.  The fundamental arguments supporting this widely accepted conclusion have been discussed in depth…”

[7] “Somatic mitochondrial DNA (mtDNA) mutations have been increasingly observed in primary human cancers…Studies reveal that mtDNA play a crucial role in the development of cancer…”

Sources

(1) Azzam EI, de Toledo SM, Little JB.  Stress Signaling from Irradiated to Non-Irradiated Cells.  Current Cancer Drug Targets, vol 4, 53-64 (2004).

(2) Zhou H, Hong M, Chai Y, Hei TK. Consequences of Cytoplasmic Irradiation: Studies from Microbeam. Journal of radiation research, vol 40, A59-A65 (2009).

(3) Ward JF, Limoli CL, Calabro-Jones P, Evans JW.  Radiation vs. Chemical Damage to DNA, Anticarcinogenesis and Radiation Protection, 321-327 (1988).

(4) Committee on the Biological Effects of Ionizing Radiation (BEIR VII). National Research Council. Health Risks from Exposure to Low Levels of Ionizing Radiation: BEIR VII Phase 2. National Academies Press, 2006.

(5) Chatterjee A, Mambo E, Sidransky D.  Mitochondrial DNA mutations in human cancer.  Oncogene, vol. 25, 4663-74 (2006).

(6) Caldicott , ed., Alvarez R – Management of Spent-Fuel Pools and Radioactive Waste, Crisis Without End. New York, NY: New Press; 2014.

(7) Bianconi E, Piovesan A, Facchin F, Beraudi A, Casadei R, Frabetti F, Vitale L, Pelleri MC, Tassani S, Piva F, Perez-Amodio S, Strippoli P, Canaider S.  An estimation of the number of cells in the human body.  Annals of Human Biology, vol 40, 463-471 (Nov 2013).

(8) Richardson R. Ionizing Radiation and aging:  rejuvenating an old idea.  Aging, vol. 1, 887-902 (2009).

Comments ( 0 )

Leave a comment.

Your email address will not be published.