Effects of High-dose Ionizing Radiation

High-dose ionizing radiation serves as an effective alternative to surgery or a valuable complement to surgery and/or chemotherapy in the locoregional treatment of head and neck malignancies. Oral healthcare providers should anticipate caring for head and neck cancer patients undergoing radiotherapy or those who have previously completed treatment. Therefore, understanding the deterministic biological changes caused by high-dose ionizing radiation is essential.^5,6,11

The therapeutic effectiveness of ionizing radiation is linked to its impact on tumor cell DNA. Radiation can damage DNA directly by inducing breaks or indirectly by interacting with water or oxygen molecules, generating ion pairs and reactive oxygen species such as H₂O₂ and hydroxyl radicals (Figure 5).¹³ If unrepaired, DNA damage is likely to result in cell death, thereby eliminating malignant activity.¹³

Figure 5.

Figure 5.

It is estimated that two-thirds of radiotherapy-induced damage to DNA is caused by hydroxyl radicals.

Malignant cells have a decreased capacity to repair radiation damage. They can fall into one of three categories: (1) lethal damage, which occurs when no DNA repair is possible and leads to cell death, (2) sublethal damage, which is repairable as a function of time provided no further radiation damage is incurred prior to the repair, and (3) potentially lethal damage, which is a condition in which cells may survive without repair, depending on post-radiation conditions.¹³

The radiation dose is defined as the amount of energy absorbed by the irradiated tissue. The unit of absorbed dose is the Gray (Gy = 1 J/kg). A standard radiotherapy regimen for head and neck neoplasms involves administering 60–70 Gy, fractionated at a rate of 2.0 Gy per day, 5 days per week, over 6 to 7 weeks. However, newer and often more aggressive protocols and techniques may be utilized to enhance tumor control and/or minimize side effects.¹³

In theory, any malignant tumor can be eradicated by ionizing radiation if a sufficiently high dose is delivered. The primary limiting factor is the tolerance level of the surrounding normal tissues.¹³ These adverse effects can be classified as either direct, meaning radiation-induced destruction or damage to vulnerable cells resulting in tissue function loss or disruption, or indirect, meaning radiation-induced reductions in vascularity and related tissue alterations.^5,6,8

Short-term effects - Undifferentiated cells within irradiated tissues or organs will sustain severe damage, leading to an acute but temporary disruption of their integrity and function. If radiation doses are relatively low, stem cells may eventually differentiate, facilitating healing and at least partial restoration of tissue or organ function.^5,6,8

Long-term effects - In some cases, radiation therapy delivers doses high enough to compromise the microvasculature of tissues and organs without directly harming differentiated cells. This damage typically becomes evident 6–8 weeks after irradiation. The resulting vascular impairment leads to reduced nutrient supply to affected organs, ultimately causing degeneration and necrosis. These effects continue to progress throughout the remainder of the patient’s life.^5,6,8