Characteristics of Radon-222

Fate and Transport

Monitoring in the Environment


Measurement Methods

Control and Prevention

Harmful Effects

Absorption, Distribution and Organic Sites of Toxicity

Radon Dose

Radon Biomarkers

Risk Assessment

Molecular Action and Genetic Effects

Radon for Skeptics

Radon for Children

Overview of the Ionization Process

Ionizing Radiation consists of alpha, beta and gamma particles:

Alpha radiation is simply helium nuclei, that is, each particle consists of two protons and two neutrons. Because the nuclei have no electrons, they have a +2 charge. Because of its mass, alpha radiation will not penetrate healthy skin or even a piece of paper. However, if alpha radiation enters the mouth or nose, it may cause cancers in lungs or other organs.

Beta radiation consists of electrons. They have negative charges. Because they are energetic and have no rest mass, they can be more of a potential health threat than alpha radiation. Beta radiation may penetrate 1-2 cm of human flesh, but may be stopped by a few millimeters of aluminum or glass.

Gamma radiation is closely related to X-rays. Like light, gamma radiation consists of photons. Gamma rays are extremely energetic and potentially dangerous. Gamma radiation readily passes through the human body and can only be stopped with lead or concrete.

Most atoms are electrically neutral; they have the same number of positively charged protons in their nucleus as negatively charged electrons orbiting the nucleus. However, when ionizing radiation passes through a material, it can transfer some of its energy to an electron; this “knocks” the electron out of its orbit. The free negative electron leaves behind a positively charged ion. This process is called ionization.

Ionization of an Atom

Source: The Ohio State University Extension

Knowing about ionization is important for two reasons.

  • First, internal and external radiation emission can cause both short-term and long-term health consequences.
    Second, because ions have an electrical charge, they are easy to detect. This makes it possible to measure the amount of radiation present — even at extremely low levels.

Specific Genetic Damage Caused by Radon

Most of the epithelial cellular damage is not from radon gas itself, which is removed from the lungs by exhalation, but from radon's short-lived decay products (half-life measured in minutes or less). When inhaled, these decay products may be deposited in the airways of the lungs and subsequently emit alpha particles as they decay further. The total amount of energy emitted by the progeny is several hundred times that produced in the initial decay of radon. The increased risk of lung cancer from radon primarily results from these alpha particles irradiating lung tissues. When an alpha particle passes through a cell nucleus, DNA is likely to be damaged. More specifically, available data indicates that alpha particle penetration of the cell nucleus may cause genomic changes typically in the form of point mutations and transformations.
Since alpha particles are more massive and more highly charged than other types of ionizing radiation, they are more damaging to the living tissue. As previously described, alpha radiation travels only extremely short distances in the body. Thus, alpha radiation from decay of radon progeny in the lungs cannot reach cells in any other organs, so it is likely that lung cancer is the only major and likely cancer hazard posed by radon.

By breaking the electron bonds that hold molecules together, radiation can damage human DNA, the inherited compound that controls the structure and function of cells. Radiation may damage DNA directly by displacing electrons from the DNA molecule, or indirectly by changing the structure of other molecules in the cell, which may then interact with the DNA. The latter mechanism will be described in more detail later. When one of these events occurs, a cell can be destroyed quickly or its growth or function may be altered through a change (mutation) that may not be evident for several years.

At low radiation doses, however, the possibility of such a change causing a clinically significant illness or other problem is believed to be remote.

Genetic Damage from Radiation

Source: U.S. Environmental Protection Agency

In addition, cells have the ability to repair the damage done to DNA by radiation, chemicals, or physical trauma. The effectiveness of these cellular repair mechanisms depends on the kind of cell, the type and dose of radiation, the individual and other biological factors.

An alpha particle emitted from radon daughter decay is in the form of a high energy helium ion, He2+. These helium particles transverse cell nuclei in a linear pattern and deposit energy in a fashion known as LET. LET, otherwise known as Linear Energy Transfer, refers to the energy transferred per unit of path traveled by the ionizing particle. Since alpha particles travel short distances and are slow compared to beta and gamma particles, their efficiency in transferring energy and affecting genomic change is very high, as is their LET quantity. Once deposited, this energy causes DNA alterations, cell cycle stress, and occasional cell death. Epithelial cellular changes caused by the alpha particle emission from a single radon daughter can be seen on a microscope.

Cell death caused by radiation

Source: U.S. Environmental Protection Agency

Differences in genomic damage occurs based on whether exposure exists at either high or low doses. The most common form of alpha particle exposure is that stemming from a single particle (radon daughter) and cell interaction. At low or even moderate radon exposures, typical of those in homes, a lung epithelial cell would rarely be traversed by more than one alpha particle per human lifespan. As exposure decreases, the insult to cell nuclei that are traversed by alpha-particles remains the same as at higher exposures, but the number of traversed nuclei decreases proportionally. As already stated, there is good evidence that a single alpha particle can cause major genomic changes in a cell. These particles can cause a wide array of mutations, transformations, and DNA transversions. While some of the interactions are readily repaired before replication ensues, in order to prevent the inheritance of any DNA alterations, others are much more cytotoxic and can be deadly for the cell. Since a second transversion by an alpha particle across a cell would alter its DNA in a fashion similar to the first, it is likely that the cell could not survive and apoptosis (cell death) would ensue. This being the case, genomic changes would not be transferred in cellular replication because the cell would not live to reach that stage. Therefore, the associated death of cells and alpha-particle exposure creates an inverse dose-response effect at high doses, where, as the rate of exposure increases, the rate of increasing severity of the toxic effect decreases.

Even allowing for a substantial degree of repair, the passage of a single alpha particle has the potential to cause irreparable damage in cells that are not killed. If not repaired, DNA damage from the Linear Energy Transfer in this type of interaction can be preserved and incorporated into the genetic structure of transcribed DNA. Since LET induced DNA mutations can sometimes exist through 50 cellular generations, at which point the mutational insult becomes too cytotoxic for the cell to continue replication, tumor progression is an inevitable response. In addition, there is convincing evidence that most cancers are of monoclonal origin, that is, they originate from damage to a single cell. These observations provide a mechanistic basis for a linear relationship between alpha-particle dose and cancer risk at exposure levels at which the probability of the traversal of a cell by more than one alpha particle is very small, that is, at exposure levels at which most cells are never traversed by even one alpha particle. These mechanistic considerations and a lack of credible evidence to the contrary were the basis for the adoption of a linear-non-threshold model for the relationship between radon exposure and lung-cancer risk. However, the possibility of a threshold relationship between exposure and lung cancer risk at very low levels of radon exposure cannot be excluded.

Health Effects Caused by Reactive Oxygen Species

Researchers from the Los Alamos National Laboratory identified a new mechanism by which radon exposure may cause toxic health effects. This latest study investigates the possibility that alpha particles emitted by radon produce reactive oxygen species (ROS) that are chemically very reactive. These intermediate molecules damage nucleotide bases and form DNA lesions as secondary bi-products of formation. Therefore, these molecules could be the source of damage within a cell that sparks the onset of cancer. The researchers quantified the rate of cellular production of these two highly reactive oxygen molecules:

  • superoxide-an electrically charged pairing of oxygen atoms (O2-2)\
  • hydrogen peroxide (H2O2)

Such products are especially harmful in the body because they can persist and continue to cause mutations in DNA. Additionally, because of their potential for redox-cycling and other various pathway mechanisms causing base alterations, ROS are key components leading to oxidative stress. The observations negate pre-existing assumptions that alpha particles like those emitted by radon and radon progeny exert their genetic changes exclusively through direct traversals of cell nuclei. Their work suggests that even interactions of alpha particles with the fluids lining the lungs may lead to alterations in the DNA of nearby cells.

The Los Alamos researchers studied normal human lung cells grown in a culture medium and exposed them to different amounts of alpha radiation. They then used flow cytometry (a tool used in molecular quantitation) to discern the amount of superoxide and hydrogen peroxide that formed.

The researchers learned that exposure to low doses of alpha emission increased the production of the reactive oxygen species superoxide and hydrogen peroxide within the cells. Although the response rate of superoxide production to the amount of the alpha dose was not linear, superoxide production increased significantly with alpha-particle exposure even at the lowest doses. Similar increases in cellular production of the reactive oxygen species were found with cells that were not directly irradiated but, instead, were treated with culture medium that had been exposed to a low dose of alpha particles.

The research team determined where alpha particles hit the cells and showed that a direct hit on the nucleus was not necessary to generate production of hydrogen peroxide. The team also irradiated the medium itself and found that it produced reactive oxygen forms. This suggests that even irradiation of material surrounding cells can create a potentially destructive environment. Extensions to these findings into an in vivo condition would suggest that inhaled radon and radon progeny may induce a condition of oxidative stress that is transmissible among lung cells and that may be involved in mediating DNA damage.

DNA Damage and Repair Mechanisms

Single strand breaks (SSB) occur when one of the two strands on the DNA double helix are broken, and are a common effect of all types of ionizing radiation. Interstrand crosslinks, DNA-protein crosslinks, base deletions, or nucleotide rearrangements can also result from exposure to ionizing radiation. Once altered in any of these manners, the DNA is repaired via one of three mechanisms, depending on the type and extent of damage:

  • NER (Nucleotide Excision Repair)
  • BER (Base Excision Repair)
  • MMR (Mismatch Repair)

These repair processes involve a series of steps where the DNA alteration is identified by scanning enzymes, the adduct of a problem site is removed, and the strand is ligated together by sequence and base specific enzymes to reform the double helical structure.

Double strand DNA breaks (DSB) are also a possible consequence of exposure to ionizing radiation. This is considered to be the most toxic genetic effect associated with ionizing radiation. DSB occurs when both phosphate backbones of the DNA double helix are broken. In addition to the genotoxic effects of the breakage, non-specific repair of DNA DSB's can lead to mismatched ends being ligated together. This event would generate a secondary toxic effect by creating an altered sequence which may prevent successful cellular replication. Mechanisms for double strand breakage repair take two forms, homologous and non-homologous recombination.

Homologous recombination of a DNA double strand break is pictured on the left side of the figure to the right. This repair mechanism requires extensive regions of sequence homology, which are found on either the sister chromatid or the homologous chromosome. The first step in the mechanism involves processing of both the 3' ends of broken DNA sequence to generate single stranded tails. Using the sequence information from the homologous regions of the sister chromatid or homologous chromosome, the strands are exchanged. Finally, DNA synthesis ensues in order to restore the original structure of the helix before the DSB occurred.

Non-Homologous double strand break repair, pictured on the right side of the figure to the right, does not need any sequence homology information to rejoin the ends. This mechanism involves processing and interaction of the sheared ends first by a nuclease and then by a heterodimer. These molecules will tag the DNA and target DNA dependent protein kinases to recognize the damaged site and assist in ligating the ends back together. This process involves several proteins (listed in the figure) and can sometimes create a mismatch of DNA broken ends. Therefore, non-homologous repair may result in an unintentionally altered DNA strand, which can prove toxic during cellular replication.

Another functional piece of the repair process involves a change in the rates of cell cycling after alpha particle radiation interaction. This will occur following genetic damage or the accumulation of ROS. Accumulation of the tumor suppresser gene, p53, in the nucleus of a cell after strand breaks, has been found to cause prolonged S-phase termination followed by inhibited G2-phase onset. This results in an increased time period in which DNA repair processes can work. Since, at this point in the cycle, transcription and replication have not yet occurred, cycle stalling serves as a method of enabling the repair of DNA lesions before they are inherited to a daughter cell.

Possible Teratogenic Effects Caused by Radon Exposure
Alpha particle exposure through early life stages may have profound effects on the health and survivability of an embryo or fetus. If dissolved in a mother’s blood stream in the uncharged phase, radon can pass through the placenta and into the developing child. If the developing child is only in the embryo phase, and a radon particle forms a progeny and deposits anywhere, emitting alpha radiation, the formation of DNA lesions will most likely kill it. At such an early point in human development, the presence of inheritable DNA adducts or lesions causes too much genomic instability to allow for a viable organism. On the other hand, if the developing child is in the fetal stages, most of the bodily development has already occurred. In this case, a radon particle passing into the fetus would likely move to lipid portions of the unborn child, namely the brain and other organs. Since brain development is most crucial in this phase, ionizing radiation at this point might not kill the organisms but may cause severe inhibition in brain development leading to mental retardation after birth. Exposure of radon to a developed child after the first year of birth, when the brain is less lipid-like and the blood-brain-barrier is fully formed, follows the same pathways as for adults. Exposure to children, however, means they have a much longer time than adults to allow for the progression of DNA lesions to form their toxic endpoints.

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