We are routinely exposed to radiation. Simply, radiation is the propagation of energy in the form of waves or particles through material in space (Mu et al., 2018). The world is full of background radiation to which we are constantly exposed. Everything we see and hear comes to us in the form of radiation.

Radiation is mainly of two kinds: ionizing radiation (IR) and non-ionizing radiation (NIR). There are many differences between IR and NIR, but what truly distinguishes them is their ability to remove electrons from the atoms or molecules of the target material (Mu et al., 2018). IR is energetically higher than NIR. NIR has enough energy to move and rotate atoms, without altering their structure. IR on the other hand is highly energetic and once it hits the material, it kicks off tightly bound electrons, converting atoms to ions, hence the name Ionizing Radiation. The figure below summarizes the main sources of NIR and IR, and the position of the visible spectrum (“light that we see”) within the range of radiation.

Radiobiology is dedicated to the study of the impact of radiation on living things. For the last decades, the effects of IR have been intensively studied, resulting in an increased recognition of its risks, but also the potential benefits of its use such as in cancer radiotherapy. The purpose of this post is to help you appreciate the perks of radiobiology and how it helped us to understand the risks and potential benefits of IR.

The Impact of Radiation on Human Health

Planet Earth is full of radiation. Our exposure to low-dose, background radiation is constant. Man-made sources of radiation are increasingly common, such as tv, radio, x-ray machines, and nuclear energy. The ability of IR to ionize atoms poses a health risk, as IR can penetrate skin and other tissues, and attack essential components of cells such as lipids, proteins or even DNA (American Cancer Society, 2015). IR can lead to oxidation of cellular components and induce DNA breaks, which are damaging to the cells and are deeply linked to cancer development. The type of damage depends of the IR source, the radiation dose (high versus low), the exposed area, and the duration of the exposure (Streffer & Herrmannn, 2012; U.S. Food and Drug Administration, 2019).

The health effects of IR can be cancer and noncancer-related. Radiobiology has clearly shown that cancers from the lungs, skin, breast and thyroid are highly associated with exposure to both high-dose and low dose IR. Acute exposure to high dose IR may lead to the rapid development of cancer, due to extensive DNA damage in the irradiated cells. Similarly, exposure to low-dose IR is associated with development of cancer, namely from the thyroid and skin. However, in the latter case, cancer develops with higher latency periods, due to chronic exposure to low-dose IR (Mu et al., 2018). Noncancer consequences of irradiation include cardiovascular and Alzheimer diseases, cataracts, congenital malformation and sterility (in case of irradiation of reproductive organs) (Hamada et al., 2014). Acute radiation syndrome (ARS) occurs when a part or whole-body is subjected to irradiation, as it happens in cases of nuclear disasters or atomic bombings. ARS can be multisystemic and present with radiation skin burns, gastrointestinal and metabolic effects (such as nausea and diarrhea), central nervous system impairment (damage to the nerves and convulsions), and internal bleeding and premature death (which can occur as fast as 48h post-irradiation in cases of severe acute exposure) (Centers for Disease Control and Prevention, 2018).

So, Why do we Keep Exposing Ourselves to Radiation?

This seems like a reasonable question, after all. Why would we voluntarily keep exposing ourselves to IR? The ability of IR to ionize can be used with enormous benefits for human health, if its use is properly regulated. IR is consistently used in medical practice in the diagnosis and treatment of several diseases including cancer, improving premature diagnosis and survival rates (Boustani et al.,, 2019; Zeman, 20112). The use of radiotherapy is one of the best-known examples of IR use in the medical setting. A fundamental principle of radiotherapy is fractionation, meaning that patients are exposed to a certain amount of radiation, divided by several sessions in which they are exposed to smaller radiation doses. By controlling fractionation, timing and dose, physicians and radiobiologists are able to improve the effectiveness of radiotherapy, maximizing IR-induced damage in cancer cells, and minimizing the damage to healthy cells (Boustani et al., 2019).

The 4 R’s of Radiobiology

The cytotoxicity of radiotherapy results from physical, chemical, and cellular damage to cancer cells. When a tumor is exposed to IR, water molecules are ionized, creating reactive species – radicals – that are highly reactive and inflict DNA damage. Cells have a complex system of repair, however, in cancer cells, this system is often perturbed due to mutations. Therefore, compared to healthy cells, cancer cells do not repair effectively from the damage of IR, which results in the accumulation of DNA damage that ultimately leads to cell death. Radiobiology defines specific factors that determine how tissues and cells respond to IR:

• Reoxygenation: well-oxygenated tissues are more sensitive to radiation than poorly oxygenated ones.
• Redistribution: the response of cells to radiation varies according to their stage of the cell cycle, and actively dividing cells are more sensitive than non-dividing ones. In a radiotherapy session, only the dividing cells (in the G2 or mitotic phase of the cell cycle) will be killed, and nondividing cells will continue proliferating. In the next session, similarly, the dividing cells will be killed. With sufficient radiotherapy sessions all cancer cells will be eventually “caught” in their dividing, IR-sensitive phase.
• Repopulation: refers to the increase of cell proliferation after irradiation. This phenomenon can occur in both normal and malignant cells. Some tumor cells show increased repopulation after 4-5 weeks of treatment. When this happens, treatment parameters like fractionation, time, and dose must be corrected to minimize the effect in the following treatments.
• Repair: refers to the capacity to recover from radiation-induced damage. In cancer cells the repair system is often impaired, leading to increased cell death when compared to healthy cells.

Recently, Radiosensitivity was added to the list of radiobiology R’s. Radiosensitivity refers to the intrinsic sensitivity of a tumor to radiation, which depends on specific factors such as the tissue of origin, mutations, previous radiotherapy and chemotherapy treatments, among other factors.

Are All Ionizing Radiation the Same?

As we said earlier, IR is the type of radiation that can kickoff electrons from atoms, forming electrical charged ions – radicals. However, the way IR propagates and affects the material is distinct. The table below summarizes the main kinds of IR, their sources, and their capacity to penetrate the human body in case of external exposure.

The most common form of exposure to α-particles is through the inhalation of radon gas, which is linked to higher risk of lung cancer development. Radon gas is formed from the radioactive decay of uranium, thorium or radium, which are heavy metals present in rocks, soil and water (Centers for Disease Control and Prevention, 2019).

β-particles result from the decay of radioactive elements. Because of their low energy, external exposure to β-particles is only relatively damaging. However, due to their small size, β-particles are easily propagated in the air, water or food. Inhalation or ingestion of any kind of radioactive source constitutes an internal exposure. Internal exposure to β-particles is much more dangerous than external exposure, due to the proximity to internal organs and tissues (MSD Manual – Professional Version, 2019).

Particle radiation, i.e., α and β radiation, is propagated in the form of particles. Due to their size and mass, particle radiation has relatively low energy and ionizing power than wave radiation, i.e., gamma and X-rays. Gamma and X-rays are radiation that propagates in the form of waves of photons, which are produced along with α and β particles. Gamma rays are extremely dangerous, due to their high energy and their capacity to penetrate deeply in the human body, ionizing molecules through its passage. Similar to the better-known X-rays, gamma rays have been used in radiotherapy.  This kind of radiation has also been used in sterilization techniques to kill bacteria as an alternative to chemical treatments (MSD Manual – Professional Version, 2019; Mu et al., 2018; Zeman, 20112).

Is Radiation Measurable? How can we do it?

Radiobiology research led to the development of a universal system to measure radiation, which includes four parameters: radioactivity, exposure, absorbed dose, and equivalent dose (acronym R.E.A.D.) (“United States Nuclear Regulatory Commission,” 2017).

• Radioactivity refers to the amount of IR released by a certain material, independently of the type of IR emitted. The expression unit is the curie (Ci) or the Becquerel (Bq);
• Exposure refers to the amount of radiation traveling through space. The expression unit is the roentgen (R) and the coulomb/kilogram (C/kg);
• Absorbed dose refers to the amount of radiation absorbed by the material when radiation travels through it. The expression units are the radiation absorbed dose (rad) or the gray (Gy)
• Equivalent dose (or effective dose or biological risk) considers the type of radiation and expresses a combination of the absorbed dose and the medical effects of it. The expression units is the roentgen equivalent man (rem) or the sievert (Sv).

The table below summarizes the equivalent dose for each type of IR. To calculate the equivalent dose, a radiation weighting factor (W_R) that takes into account the IR type is used. ɑ particles exhibit high ionization capacity, making their W_R highest among other IR types. This means that for any dose (D) of absorbed ɑ-particles, for the exposed tissue it will correspond to an equivalent dose (H) 20 times higher.

H = D ✕ W_R

1 R (exposure) = 1 rad (absorbed dose) = 1 rem (equivalent dose)

Make the SafestUuse of Ionizing Radiation in your Healthcare

Advances in radiobiology have shown that radiotherapy changes tumor microenvironment and induces local and systemic immune responses. As we’ve seen, specific parameters help doctors to predict tumor response to IR, and to adapt therapy regimens to patients. Moreover, several drugs have been developed to enhance the cytotoxic effects of radiation in cancer treatment, and to protect surrounding healthy tissues from radiation damage. Radiosensitizers are potentiators of radiation cytotoxicity. When used in combination with radiotherapy, radiosensitizers induce a combined cytotoxic effect higher than would be expected by the simple addition of expected single effects. Examples of radiosensitizers are 5-bromodeoxyuridine and misonidazole (Zeman, 20112). Radioprotectors on the other hand, are compounds that reduce radiation damage in normal tissues by capturing highly reactive radicals produced by IR in cells. Radioprotectors exhibit antioxidant properties, and are ministered before or together with radiotherapy, which is essential for their effectiveness. The most widely used radioprotector in cancer therapy is amifostine.

Final Words

In the last few decades, scientific advances in radiobiology research resulted in a safer use of radiation by humans. From energy generation to communication technologies, radiation is all around. In the clinical setting, ionizing radiation is used in the diagnostic and treatment diseases like neurodegenerative disease and cancer. Given the associated health risks of IR for human health, methods for predicting the optimal exposure dose for each patient, that comes with minimal injury, have been developed. Together with enhancers and radioprotectors, the use of IR in the clinical setting is now more efficient and safer than ever before.

References

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