A 35-year-old, previously healthy man is evaluated immediately after accidental exposure to ionizing radiation at a fluoroscopy manufacturing facility. The patient is currently asymptomatic. Vital signs are normal. Physical examination shows no abnormalities. If radiation exposure is significant, which of the following cells are most likely to be affected first?
Exposure to ionizing radiation causes cell injury directly through DNA double-strand breakage and indirectly through the generation of free radicals that can damage DNA and other cellular components. Significant DNA damage results in the upregulation of p53, which inhibits replication and induces apoptosis of the affected cell.
The effects of ionizing radiation vary based on the rate of cellular division. Highly proliferative cells (eg, stem cells) have less time to repair radiation-induced DNA damage before cell death occurs. Therefore, these cells are highly sensitive to ionizing radiation and most likely to be affected first following exposure.
Intestinal crypt stem cells divide continuously to produce new intestinal epithelial cells, which have a short life span and are completely renewed every 3-5 days. Rapid denudation of the gastrointestinal mucosa can occur if the radiation dose is significant, resulting in nausea/vomiting, diarrhea, and gastrointestinal bleeding.
Other cells that are highly sensitive to the effects of ionizing radiation include the following:
(Choices A and D) Bladder epithelial cells and renal proximal tubular epithelial cells have a much slower turnover rate (eg, weeks to months) compared with intestinal epithelial cells and are less likely to be affected first by exposure to ionizing radiation.
(Choices B and E) Cardiac and skeletal myocytes are long-lived, differentiated cells that do not rapidly divide and can more effectively repair radiation-induced DNA damage before cell death occurs.
(Choice F) Although type II pneumocytes can dedifferentiate and proliferate in response to injury to replace type I pneumocytes, they have a low rate of proliferation at rest and are less likely to be affected acutely by exposure to ionizing radiation.
Educational objective:
Ionizing radiation induces DNA damage (eg, double-strand breakage, free radical generation) that predominantly affects highly proliferative cells (eg, skin stem cells, hematogenous progenitors, intestinal crypt cells). These rapidly dividing cells are the first to be lost following significant radiation exposure, resulting in hair loss, pancytopenia, diarrhea, and nausea/vomiting.