Medical Radiology - Lazar A.P. 2008

Radiation Therapy
Biological Effects of Ionizing Radiation

All Types of ionizing radiation act in the same way: they transfer their energy to the atoms of matter, causing ionization. However, the distribution of energy within the matter depends on the type and energy of the particles and photons. Alpha particles quickly lose their energy as they travel through a medium, forming dense clusters of ions along their trajectory; in other words, they have a high linear energy transfer. Electrons produce relatively scattered ion pairs along their path. Photons create an even less dense ionization. Photons with energies up to 1 MeV (mega-electron volt) yield maximum Absorption in the surface layer of a living object (up to 0.5 cm). Deeper down, the photon flux weakens, leading to a decrease in the number of ions. Photons with energies exceeding 1 MeV produce maximum ionization deeper within the Tissues—the greater their energy, the deeper the maximum.

The initial stage of the biological action of ionizing radiation is a physical process of radiation interacting with matter. All types of ionizing radiation induce the excitation or ionization of atoms. As a consequence, excited and ionized atoms and molecules with high chemical reactivity appear in the tissues. They interact with one another and with surrounding atoms, generating A large number of highly active free radicals and peroxides. If a molecule is imparted substantial energy, it may fracture into fragments, producing radicals with unsaturated bonds. This process is termed radiolysis.

During the radiolysis of Water, a molecule is ionized by a charged particle, thereby losing an electron:

Class="center">→ Н₂О → Н₂О⁺ + е^-

The "ejected" electron interacts with surrounding water molecules, generating a highly excited H₂O* molecule, which subsequently dissociates to yield two radicals, H⁺ and OH^-:

Н₂О⁺ + е^-→ Н₂О* → Н⁺ і ОН^-.

These free radicals contain unpaired electrons and thus exhibit exceptionally high reactivity.

In the presence of oxygen, other radiolysis products with oxidizing properties are formed: the hydroperoxyl radical HO₂*, hydrogen peroxide H₂О₂, and atomic oxygen:

1) Н⁺ + О₂ + е^-→ НО₂ ;

2) НО₂* + НО₂* → Н₂О₂ + 2О.

In living Cells, this process proceeds much more complexly than during the irradiation of water, owing to the presence of large organic molecules that are damaged either by the direct action of radiation or by water radiolysis products. The resulting organic radicals likewise possess unpaired electrons and are extremely reactive. Their reactivity leads to the Cleavage of chemical bonds in vital macromolecules.

Morphological and functional cellular changes manifest within the very first minutes and hours following irradiation. The formation of products foreign to the Organism leads to its intoxication. At a high radiation dose, the mass of ions can cause death "under the beam." At a lethal radiation dose (for the entire human body, this is 6–8 Gy delivered instantaneously), 10¹⁵ ion pairs are formed in every gram of tissue.

Up to 75% of the water in a solution is incorporated into the Hydration shell of molecules, which likewise alter their properties under METABOLISM/18.html">The Influence of ionizing radiation. Complex molecules may rupture not only at the point of particle incidence. Energy can migrate along the molecule and trigger a break at a weak bond site. A cleaved polyatomic molecule loses its properties, and the generated radicals can attach to other intact molecules, causing them to split and yield two additional radicals capable of interacting with further molecules. This constitutes a self-accelerating chain reaction. The greater the number of molecules, the higher the probability that they will be ionized, excited, or cleaved. Given that not all cellular molecules are functionally equivalent, damage to different molecules will have varying consequences. Damage to vital Nucleoproteins (DNA, RNA)—which regulate Cell Division and metabolic processes—can result in the loss of The Cell's ability to divide and ultimately lead to its death.

Alterations in the chromosomal apparatus of a cell reflect upon its hereditary properties, resulting in radiation-induced Mutations (point mutations, chromosome breaks, Chromosomal aberrations, etc.). Damage to Lysosomes triggers cellular autolysis. Autolysis developing in somatic cells reduces the viability of the organism. In some cases, a cell may acquire the capacity for active, uncontrolled division, leading to the formation of malignant neoplasms. According to studies conducted primarily in Hiroshima and Nagasaki, the risk factors for Cancer development are estimated at approximately 10^-1 Sv^-1 for acute exposure, and 5×10^-2 Sv^-1 for chronic exposure.

Several levels of radiation impact on humans can be distinguished: 1) at THE MOLECULAR LEVEL—damage to macromolecules such as DNA, RNA, and Enzymes; 2) at the subcellular level—damage to cell membranes, nuclei, Chromosomes, Mitochondria, and lysosomes; 3) at THE CELLULAR LEVEL—suppression of cell division, cell death, and malignant transformation; 4) at the Tissue and organ levels—disruption of the Central Nervous system, Bone Marrow, and gastrointestinal tract; 5) at the organism level—lifespan reduction and death; 6) at the population level—alteration of genetic characteristics due to Gene and chromosomal mutations in individuals.

Cellular sensitivity to ionizing radiation depends on numerous factors: the type and dose of radiation (quantum or particle energy), the phase of the mitotic cycle, The rate of recovery processes, the degree of oxygenation, the presence of free sulfhydryl groups, and the functional state of the cell at the moment of irradiation. The Cell Nucleus is more radiosensitive compared to the Cytoplasm.

The degree of radiation-induced reactions is closely correlated with the partial pressure of oxygen in the biosubstrate, a phenomenon known as the "oxygen effect." The less oxygen present in a cell, the lower its radiation-induced damage. Reducing tissue oxygenation increases the resistance of cells and the entire organism to radiation by a factor of 2–3.

According to the Bergonié-Tribondeau law, the radiosensitivity of cells is directly proportional to their mitotic activity and inversely proportional to their degree of differentiation. Cells in a state of high metabolic activity, such as during the DNA Synthesis phase, are particularly vulnerable. Undifferentiated cells are likewise more sensitive to irradiation. Among cellular structures, DNA and chromosomes are the most susceptible to ionizing radiation. These characteristics form the basis for the THERAPEUTIC USE OF ionizing radiation in oncology.

At the same time, it should be noted that cells possess recovery systems that drive repair processes in nuclear and cytoplasmic structures. When mitosis is delayed, a portion of the cells dies immediately (interphase death), another portion dies after undergoing several mitotic divisions (reproductive death), and some cells recover (repair).

Tissues undergo changes under the influence of ionizing radiation depending on the predominance of specific cell types in their Structure. Particularly pronounced changes occur in actively proliferating tissues: lymphoid, hematopoietic, and endocrine. They perish at low radiation doses of 1–4 Gy, which manifests as anemia, leukopenia, and other disorders. Less pronounced radiation damage occurs in tissues with low regenerative capacity: bone, Cartilage, Muscle, and adipose tissue. The cells of these tissues perish at doses of 30–100 Gy. As an exception, The Nervous System exhibits high functional radiosensitivity, and noticeable neuro-reflex changes occur under radiation exposure.

The degree of radiosensitivity of Organs depends on the radiosensitivity of the tissues that compose them. Among the digestive organs, the Small Intestine is the most sensitive, while the Liver is the least sensitive. Organs that are highly radiosensitive or accumulate large amounts of incorporated radionuclides are referred to as critical organs. During irradiation, the most prominent changes occur in the nervous and immune systems, bone marrow, and digestive organs. Furthermore, Embryonic and Fetal tissues are more radiosensitive than adult tissues. One of the consequences of the irradiation of pregnant women following the atomic bombings of the Japanese cities of Hiroshima and Nagasaki was the mental and physical underdevelopment of some of their children.

At the population (species) level, important consequences of radiation exposure include its mutagenic properties. Mutations are sudden changes in genetic material that are inherited and lead to alterations in various traits of the organism. They are conventionally divided into spontaneous mutations—arising under the influence of natural environmental factors or due to biochemical changes within the organism itself—and induced mutations, caused by Mutagenic Factors. More than 99% of mutations are negative, while fewer than 1% are positive. Negative mutations lead to cell death or the acquisition of new properties, notably uncontrolled division and the appearance of malignant tumors. A radiation dose of 0.5–2.5 Sv is sufficient to double the mutation frequency. Doubling the radiation dose doubles the mutation rate. Characteristic of radiation-induced mutations are chromosome breaks, which account for up to 50% of all genetic apparatus lesions and are rarely observed in natural mutations.

The greater the number of people exposed to radiation, the higher the probability of recessive mutations appearing. Therefore, stringent radiation protection standards are applied to human population groups. While the annual dose limit for occupational workers dealing with ionizing radiation sources (Group A) in Ukraine is 20 mSv/year, for the general population (Category GD) it is set at 1 mSv/year.

The natural Background radiation is approximately 2.4 mSv/year. Whole-body irradiation of 1 Sv causes Blood changes, while 3 Sv leads to death within 30 days in 50% of cases.