Radiation Protection PDF - Ibn Khaldoun University College

Ibn Khaldoun University College M.Sc. Mustafa Majid Ibrahim Radiation Protection Department of Radiology and Ultrasound Technologies Assistant lecturer/ Mustafa M. Ibrahim third Class / second Lecture: Radiation dose-response relationships One additional point to consider is th...

Ibn Khaldoun University College M.Sc. Mustafa Majid Ibrahim Radiation Protection Department of Radiology and Ultrasound Technologies Assistant lecturer/ Mustafa M. Ibrahim third Class / second Lecture: Radiation dose-response relationships One additional point to consider is that ionizing radiation also induces a form of senescence or permanent growth arrest in which cells are still metabolically active, but reproductively inhibited. This is best exemplified by fibroblasts that when irradiated in cell culture, stay attached to plates for weeks but never divide. However, they are able to secrete growth factors and mitogens that promote the growth of tumor cells. Senescence has been largely studied in cell culture in the laboratory, and only recently has evidence been accumulating that it occurs in tissues. Tumor control probability (TCP) is plotted as a function of total dose, and the incidence of normal tissue complications is also plotted as a function of dose. What is illustrated is a favorable situation where the tumor is more radiosensitive than the normal tissue. In the case of tumor control, the shape can be explained solely by the random nature of cell killing after irradiation and the need to kill every single cell to achieve a cure. The ratio of the tumor response for a fixed level of normal tissue damage has been called either the therapeutic ratio or the therapeutic index. In the hypothetical example in Figure 1.a, there is a favorable therapeutic ratio, because a 30% probability of tumor control is possible for a 5% incidence of complications. The time factor is the one parameter that has been most often manipulated to increase this ratio; hyper fractionation, for example, produces a greater sparing of late-responding normal tissue than tumor control. Another strategy often quoted, although seldom achieved in practice, is to add a drug or radio sensitizer that potentiates the tumor control without potentiating the radiation damage to normal tissue. In practice, it does not need to be as clear-cut as this; it would suffice for the drug to increase tumor control to a greater extent than it increases normal tissue damage. This would result in a therapeutic gain. This is illustrated in Figure 1.b. The addition of the drug moves the tumor control curve to the left farther than the normal tissue damage curve; that is, the drug has greater cytotoxic effect on the tumor than on the normal tissue. Consequently, with the combined modalities, an improved tumor control probability is possible for the same probability of normal tissue injury. Radiation protection Page 1  Ibn Khaldoun University College M.Sc. Mustafa Majid Ibrahim (a) (b) Fig.1. the dose-response relationship is sigmoid in shape for both tumor control and normal tissue damage and how the addition of a drug, a chemotherapy agent. 1. Linear Dose-Response Relationships In linear dose-response relationships, an increase in dose corresponds directly to an increase in biological response. These models are often used in risk assessment, such as for cancer, where even small doses are considered to carry some risk. 2. Nonlinear Dose-Response Relationships Nonlinear relationships describe complex responses, where the intensity of the response may change disproportionately with dose. These relationships may include thresholds, indicating that a certain dose level must be exceeded before a noticeable response occurs. 3. Constructing a Dose-Response Relationship To construct a dose-response relationship, data must be collected from various experiments. This involves determining the doses used, measuring biological responses, and then analyzing the data to identify the most suitable model (linear or nonlinear). A linear-quadratic dose response is a relationship between dose and biological response that is curved. This implies that the rate of change in response is different at different doses. The response may change slowly at low doses, for example, but rapidly at high doses. A linear-quadratic dose response is written mathematically as follows: if Y represents the expected, or average response and D represents dose. Radiation protection Page 2  Ibn Khaldoun University College M.Sc. Mustafa Majid Ibrahim 𝑌 = 𝒂𝐷 + 𝒃𝐷2 Where 𝑎 is the linear coefficient (or slope) and 𝑏 is the quadratic coefficient. The Biological Effects of Radiation 1. Atomic Level: When radiation interacts with matter, it can knock electrons out of their atomic orbits, leading to ionization. This process creates positively charged ions and free electrons. In biological tissues, this ionization can result in the formation of reactive oxygen species (ROS), which are highly reactive and can damage other nearby atoms and molecules. This fundamental interaction is crucial because it sets off a chain reaction that can lead to significant cellular damage. 2.Chemical Interactions: The free radicals generated can react with essential biomolecules, particularly DNA, proteins, and lipids. When free radicals attack DNA, they can cause various forms of damage, such as base modifications, single-strand breaks, or double-strand breaks. If the cellular repair mechanisms fail to fix this damage accurately, it can lead to mutations. These mutations can either be harmless, cause cell malfunction, or lead to uncontrolled cell division, contributing to cancer development. Moreover, lipid peroxidation can compromise cell membranes, affecting cell integrity and function. 3.Cellular and Whole Animal Changes: The cumulative effect of molecular and cellular damage leads to significant biological consequences. At the cellular level, damaged cells may undergo necrosis (uncontrolled cell death) or apoptosis (programmed cell death), disrupting tissue homeostasis. If the damage promotes cancerous transformations, it can result in tumor formation, metastasis, and ultimately threaten the organism's life. On a broader scale, these effects can influence reproductive success, immune response, and lifespan. Ecosystems can also be affected; for example, populations exposed to radiation may experience declines in fertility and survival rates, impacting biodiversity. Radiation protection Page 3