Chapter 4: Biological Effects of Ionizing Radiation PDF

# Chapter 4: Biological Effects of Ionizing Radiation ## Introduction * All living organisms are made up of the fundamental unit of life, known as the cell. * Adult human beings have nearly 10¹⁴ cells of different types. * A cell is made up of different organelles: * Central nucleus...

# Chapter 4: Biological Effects of Ionizing Radiation ## Introduction * All living organisms are made up of the fundamental unit of life, known as the cell. * Adult human beings have nearly 10¹⁴ cells of different types. * A cell is made up of different organelles: * Central nucleus * Cytoplasm * Cell membrane * The nucleus contains the chromosomes which are made up of Deoxyribonucleic Acid (DNA) and basic proteins (Histone). * DNA is the genetic material of the cell. * DNA is the most important target molecule for the induction of radiation damage in cells. ## Diagram of the Cell - **Figure 4.1:** This figure shows a diagram of the human cell with a focus on the nucleus. - **Description:** The cell membrane encloses the cytoplasm which contains ribosomes, mitochondria, Golgi apparatus, lysosomes, endoplasmic reticulum (ER), and centrioles. - The nucleus is enclosed by a nuclear membrane. - The nucleus contains nucleolus, chromatin, nucleosomes, DNA, and histones within it. ## Human Body and Cells * Each organ in the human body is made up of different types of cells with specialized functions. * Some cells divide at a faster pace than others, such as bone marrow, stem cells. * Muscle and nerve cells never divide. * Cells are constantly dividing and undergoing maturation through a series of modifications. * This process is called differentiation, and it gives rise to functional cells. * The red bone marrow produces blood cells, including red blood cells, white blood cells, and platelets. ## Radiation Effects at the Cellular Level ### Mechanism of Damage * Radiation can interact with atoms in the DNA molecule or other cellular components. * This interaction is called a **direct effect**. * Radiation can also **indirectly** affect DNA by interacting with water molecules in the cell. * This interaction results in the production of free radicals (hydrogen and hydroxyl) that can damage DNA. * **Hydrogen peroxide (H2O2)** can also contribute to cell destruction. ### Internal Exposure to Radiation * Volatile and gaseous isotopes enter the human body through inhalation. * Some isotopes, like tritium, can be absorbed through the skin. * Other isotopes, like strontium-90 and iodine-131, accumulate in specific tissues. * Tritium and cesium-137 can distribute throughout the system. * **Annual Limit Intake (ALI)** of a radionuclide is the intake by inhalation, ingestion, or skin absorption that would result in a committed dose equivalent to the dose limit. ## Biological Damage Types of Radiation * **Biological Damage:** The damage done to biological material due to radiation. * **Type of Radiation:** The kind of radiation, such as alpha, beta, or gamma waves. * **Dose Rate:** The amount of radiation delivered per unit of time. * **Fractionation:** The division of the total radiation dose into smaller doses given over a period of time. * **Mechanism of Damage:** The way in which radiation damages cells, such as direct or indirect damage. ## 100mGy (10 Rad) * Is the minimum radiation exposure level that can be detected using the biological dosimeter. * This is done by examining the frequency of dicentric chromosomes in human lymphocytes. ## Nature of Damage * Ionizing radiation can cause breaks (single and double strand breaks) in the DNA molecule. * It can also cause structural changes, like base damage and cross-linking. * **Microscopic examination** of irradiated cells shows various alterations in the structure of chromosomes. * These are called **chromosome aberrations**. * Chromosome aberrations include dicentrics, deletions, transpositions, and inversions. ## Effects at the Cellular Level * Radiation can cause **lethal damage** to cells, resulting in cell death. * Radiation can also cause **non-lethal damage**, or **heritable damage **, which alters the genetic material. * This can lead to mutations in the cell. * Heavily damaged cells die during mitosis (mitotic death). * This is why damage is faster in organs with fast-dividing cells, such as bone marrow, intestines, skin, and reproductive systems. * Damage to other tissues, like eye lens, kidney, connective tissues, and liver, is delayed. ## Factors Modifying Damage * **Type of radiation:** Densely ionizing radiations, like neutrons and alpha particles, cause more damage than sparsely ionizing radiations, such as X-rays, beta rays, and gamma rays. * **Dose rate and dose fractionation:** Higher radiation doses delivered in a short period cause more damage than the same dose delivered over a longer period or in smaller doses. * **Sensitizers:** Some chemicals can increase the damage caused by radiation. * **Protectors:** Some chemicals can reduce the damage caused by radiation. * **Type of cells:** Different cells have varying abilities to recover from radiation damage. * **Ability of recovery from damage:** Cells can repair some damage if they have time. ## Effects of Radiation on Human Beings * **Somatic effects:** Effects that appear in the exposed individual. * **Genetic effects:** Effects that appear in future generations as a result of excessive exposure to the reproductive cells ### Deterministic and Stochastic Effects * **Deterministic effects** occur as a result of accidental exposure to large doses of radiation. This causes a significant number of cells to be killed, resulting in damage to organs. * Examples of deterministic effects: radiation sickness, death, and damage to skin, bone marrow, gonads, intestines, and eye lens. * These effects do not occur at low doses or following chronic exposures. * **Stochastic effects** (cancer induction or genetic effects) may occur at low doses. * The probability of these effects is very low but may increase with larger doses. * These effects are seen in occupational workers when the number of people exposed over a long period is very large. ### Radiation Sickness * This results from acute whole-body radiation exposure exceeding 1 Sv. * Symptoms include nausea, vomiting, diarrhea, lack of appetite, fever, headache, and dizziness. * The severity and time of onset of symptoms are dependent on the dose of radiation. * Symptoms appear within an hour after exposure to high doses (4-6 Sv). * Symptoms may appear after 3 hours for doses of 1-2 Sv. ### Radiation-Induced Death * **LD50/60:** Lethal dose 50/60 is the dose that kills 50% of exposed people within 60 days. * Death can result from damage to blood-forming organs, primarily bone marrow cells. * Severe damage to the intestines or central nervous system can also lead to death. ### Damage to Individual Organs * **Skin:** Doses below 6 Gy cause transient reddening of skin and hair loss (epilation). * Doses above 10 Gy cause peeling of epidermis and necrosis. * **Blood and bone marrow:** Lymphocytes are highly radiosensitive, and a dose of 4 Gy can kill 75% of them. * Bone marrow precursor cells (erythroblasts, myelocytes, megakaryocytes) are also radiosensitive, and a dose of 3 Gy can kill 90% of them. ### Effects of Radiation on the Organs: * **Reproductive System:** Acute exposure of the testes to as low as 0.2 Sv can cause temporary sterility. * A dose of 4-6 Sv can cause permanent sterility. * The human reproductive system can withstand a daily dose of 1 mSv without impairment of fertility. * Older females can suffer sterility from a dose of 2 Sv, while younger ones can show sterility only after 4 Sv. * **Endocrine Glands:** Endocrine glands are generally radioresistant in adults. * Children are sensitive to radiation, especially the thyroid, female breast during adolescence, and cartilage. ### Eye Lens * Acute radiation doses over 500 mSv or chronic doses over 1000 mSv can cause opacities in the eye lens. * These opacities can progress to become cataracts, which can impair vision. * The eye lens can tolerate a dose of 8 Gy in fractionated manner. * Cataract induction is a late effect, occurring 2-3 years after exposure. * Neutrons are more efficient in inducing cataracts than X-rays. ### Late Effects * Late effects manifest after several years. * These include skin fibrosis, keloids, lung damage, and kidney damage. * Radiation can cause life shortening in individuals who have been exposed to heavy doses. * There is no evidence of life shortening observed among other occupationally exposed individuals. ### Prenatal Effects * The sperm cells of the male fertilize the ovum (egg) of the female to form a fertilized egg (zygote). * The zygote develops into an individual over a period of 38 weeks. * The 7-week stage marks the end of the embryonic stage and the beginning of the fetal stage. * The embryo/fetus is very sensitive to radiation, especially during the first trimester (2-4 months). * Exposure may lead to prenatal death, neonatal death, malformations, and mental retardation. * ICRP recommends a dose limit of 2 mSv to the fetus during pregnancy. ## Stochastic Effects * Stochastic effects occur in individuals exposed within permissible limits of radiation. * These include cancer and genetic effects. * Cancer and genetic effects can occur as a result of exposure to other environmental agents. * **Epidemiological surveys** of radiation workers show no excess cancer risk among them. * However, there is evidence for an increased incidence of childhood leukemia among children born to parents exposed to radiation at Hiroshima and Nagasaki. * This evidence also suggests a possible increase in untoward pregnancy outcomes and childhood cancers occurring in survivor progeny. ### Carcinogenesis in Human Beings * **Carcinogenesis:** The development of cancer. * Most of the human data on carcinogenesis comes from the bombing at Hiroshima and Nagasaki and people who received high doses for therapeutic reasons. * **Radiogenic cancers** develop in the bone marrow, female breast, lungs, and thyroid. * These cancers appear after a latent period. * **Leukemia** appears between 3 to 5 years, with a peak incidence between 5-7 years. * Solid tumors appear after 10 years and the incidence continues to increase beyond 30-40 years. * Children are sensitive to leukemia and thyroid cancers. * Females are more sensitive to breast cancer than males. * The risk of carcinogenesis decreases with age at radiation exposure. * Individuals in the 10-19 year age group are 5 times more sensitive to certain types of cancer than those in the 50-60 year age group. ### Genetic Effects * Genetic effects involve changes to the genetic material that can be passed on to future generations. * Most of the data on genetic effects comes from studies performed in model experimental systems, mostly mice. * The International Commission of Radiological Protection (ICRP) estimates that 1 Gy doubles the incidence of mutations or the **doubling dose**. * The risk of genetic effects is hard to evaluate as many genetic diseases are multigenic and complex. * ICRP estimates that the doubling dose only increases the risk of genetic disorders by 10-15%. * The natural incidence of genetic disorders is 10-20% of all births. * Therefore, radiation exposure is a small contributor to the overall risk of genetic disorders. * The present levels of occupational exposure are considered safe. ## Significance of Different Levels of Radiation Exposure | Exposure | Significance | |---|---| | 1-2 mSv/yr | Background radiation level at sea level outdoors. | | 0.5-5 mSv | Most diagnostic radiological examinations | | 1 mSv/yr | Limit for non-occupational exposure | | 2.5 mSv/yr | Average occupational exposure | | 10 mGy (whole body) | Risk of leukemia - about 5 in 100,000 exposed | | 20 mSv/yr | Risk of cancer mortality - about 5 per 10⁴ exposed | | 150 mSv/yr | Limit for occupational exposure of whole body | | 500 mSv/yr | Limit for exposure of skin and extremities | | 100 mGy (whole body) | Detectable increase in chromosome aberrations | | 0.5 Gy | Threshold for induction of cataract | | 1 Gy (acute whole body) | Threshold dose for radiation sickness (5-10% of individuals exposed) | | 1 Gy (reproductive system) | 50 times annual dose limit to workers | | 2-3 Gy (acute whole body) | Threshold for epilation; Radiation sickness in most individuals exposed; Early erythema induction; Leukopenia; Death of a small percentage of individuals (10-30%) | | 3-5 Gy (acute whole body) | LD50/60 for human beings (untreated); Severe leucopoenia, purpura, hemorrhage, infection & depilation | | 6 Gy (X-rays) | Threshold for skin erythema; Permanent sterility in both males and females exposed; Whole body exposure results in death of more than 50% of individuals, even with the best care | | >6 Gy (gamma, partial body) | Threshold dose for skin erythema | | >10 Gy (skin) | Threshold dose for dry desquamation | | >20 Gy (skin) | Threshold dose for wet desquamation & necrosis | | >30 Gy (skin) | Ulceration and necrosis. | | 40-60 Gy (localized) | Total radiation dose used in fractionated radiotherapy of cancer | ## Objectives of Biological Dosimetry * To confirm or reject the findings of physical dosimeters and to distinguish between genuine and non-genuine exposures. * To detect a suspected exposure when there is no information from physical dosemeters, such as in the case of a person who is not routinely monitored or a radiation worker not wearing a badge. * To provide reassurance to those who are false positive on physical dosemeters which got exposed while being not worn; or maliciously irradiated. * To detect the average dose to the body in the case of very non-uniform exposures. In such situations the dosemeters may indicate a very high or low dose depending upon the irradiation geometry. * To distinguish between protracted and acute exposures in accidents. CAA provides a purely biological response taking into consideration the duration of exposure and accounting for the possible repair of radiation damage. * To detect the dose to the exposed part of the body and the fraction of the body exposed, in accidents involving inhomogeneous exposure (Partial-body, or localized). Dispersion analysis of the chromosome aberration data indicates the deviation from a Poisson distribution, which in turn is a measure of the non-uniformity of exposure. * To assist the triage of victims in accidents involving large number of exposed individuals. In the medical management of radiation accidents CAA can serve as a reliable prognostic indicator.