Effects of High-dose Ionizing Radiation

High-dose ionizing radiation is an effective alternative to surgery or a valuable adjunct to surgery and/or chemotherapy in the locoregional treatment of head and neck malignancies. Oral healthcare providers can expect to be called on to care for patients with head and neck cancer undergoing radiotherapy or who may have previously completed radiotherapy. Consequently, it is important to understand the deterministic biological changes due to high-dose ionizing radiation.5,6,11

The therapeutic benefit of ionizing radiation is related to its effects on tumor cell DNA. Radiation can interact with and damage DNA directly by causing DNA breaks or indirectly by interacting with water or oxygen molecules resulting in the formation of ion pairs and reactive oxygen metabolites such as H2O2 and hydroxyl radicals (Figure 5).13 DNA damage, if not repaired, will likely cause cell death and eliminate malignant activity.13

Figure 5.
hydroxyl radicals
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, which may be classified in one of three categories: (1) lethal damage, which occurs when no DNA repair is possible and it 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

Radiation dose is expressed as the absorbed energy by the irradiated tissue. The unit of the absorbed dose is the Gray (Gy=1 J/Kg).13 A conventional radiotherapy regimen for head and neck neoplasms consists of delivering 60–70 Gy, fractionated at a rate of 2.0 Gy/day, 5 days/week, for 6 to 7 weeks.13 However, newer and often more aggressive protocols and techniques may be employed with the goal of improving tumor control and/or reducing side effects.13

Theoretically, any malignant tumor can be destroyed by ionizing radiation if the dose delivered is sufficient. The limiting factor is the amount of radiation the adjacent normal tissues will tolerate.13 These negative effects can be either direct, i.e., radiation-induced destruction or damage to susceptible cells causing a loss or disruption of tissue function; or indirect, i.e., radiation-induced decrease in vascularity and associated tissue changes.5,6,8

Short-term effects - Undifferentiated cells of irradiated tissues or organs will be severely damaged. This will lead to an acute but transient disruption of the integrity and function of affected tissues or organs. If the doses are relatively low, after a period of time the stems cells will be able to differentiate and healing will take place followed by at least partial re-establishment of tissue or organ function.5,6,8

Long-term effects - In radiation therapy, sometimes the radiation doses are high enough to cause damage to the microvasculature of tissues and organs without damaging the differentiated cells. The outcome of this damage will be noticed 6-8 weeks post irradiation. The damage to the microvasculature will lead to a loss of nutrient flow into the organs leading to their degeneration and necrosis. These effects progress for the remainder of the irradiated patient’s life.5,6,8