Radiation dose determines tissue destruction primarily by the amount of energy deposited in cells and tissues, which causes damage at the molecular and cellular levels. When radiation interacts with biological tissues, it transfers energy that can break chemical bonds, especially in DNA, proteins, and cellular membranes. The extent of tissue destruction depends on the dose—the higher the dose, the more severe the damage, leading to cell death and tissue injury.
At low doses, radiation may cause minor damage that cells can repair, but as the dose increases, the damage overwhelms the cell’s repair mechanisms. This leads to irreversible injury such as DNA double-strand breaks, disruption of cellular membranes, and oxidative stress caused by reactive oxygen species (ROS). These effects can trigger apoptosis (programmed cell death) or necrosis (uncontrolled cell death), resulting in tissue destruction.
Different tissues have varying sensitivity to radiation depending on their cell types and rates of cell division. Rapidly dividing cells, such as those in bone marrow, gastrointestinal lining, and skin, are more radiosensitive and thus more prone to destruction at lower doses. For example, a moderate dose of radiation can cause skin erythema (redness) and later ulceration, while higher doses can severely impair bone marrow function, leading to decreased blood cell production and increased risk of infection and bleeding.
At the cellular level, radiation causes mitochondrial dysfunction by disrupting mitochondrial membrane potential and increasing membrane permeability. This leads to swelling, rupture, and oxidative stress within mitochondria, which further amplifies cell damage and death. Radiation also induces the release of mitochondrial DNA into the cytoplasm, activating inflammatory pathways that contribute to tissue injury, such as bone marrow suppression.
Radiation dose also influences the type of tissue response. Lower doses may cause transient effects like mild inflammation or temporary cell cycle arrest, while higher doses cause permanent damage such as fibrosis, necrosis, or organ failure. For example, doses above 6 Gy to the skin cause immediate reddening, followed by blistering and ulceration at higher doses. Similarly, doses above 8 Gy to the whole body can cause fatal bone marrow failure.
In addition to DNA damage, recent research highlights that radiation can damage other critical cellular structures like the plasma membrane. Damage to membranes affects cell signaling and integrity, contributing to cognitive and behavioral deficits observed after radiation exposure, especially in the nervous system.
The severity of tissue destruction is also influenced by the radiation type (alpha, beta, gamma, X-rays, neutrons) and dose rate. High linear energy transfer (LET) radiation, such as alpha particles, causes dense ionization tracks leading to more severe localized damage compared to low LET radiation like X-rays.
In summary, radiation dose determines tissue destruction through a complex interplay of direct DNA damage, oxidative stress, mitochondrial dysfunction, membrane disruption, and inflammatory responses. The higher the dose, the more extensive and irreversible the tissue injury, with rapidly dividing tissues being the most vulnerable. Understanding these mechanisms helps guide radiation therapy, radioprotection, and management of radiation injuries.