Leukemia is often linked to radiation exposure because radiation can cause significant damage to the DNA within blood-forming cells in the bone marrow, leading to mutations that disrupt normal cell growth and division. This disruption can result in the uncontrolled proliferation of abnormal white blood cells, which is the hallmark of leukemia.
Radiation, especially ionizing radiation, has enough energy to penetrate cells and directly damage the DNA by breaking chemical bonds. It can cause complex DNA damage such as double-strand breaks and clustered lesions that are difficult for the cell to repair properly. When these breaks occur in the stem cells of the bone marrow, which are responsible for producing blood cells, the damage can lead to mutations in genes that regulate cell cycle, apoptosis (programmed cell death), and DNA repair mechanisms. If these mutations accumulate, they can cause the cells to grow uncontrollably and avoid normal death signals, leading to leukemia.
Moreover, radiation exposure generates reactive oxygen species (ROS), highly reactive molecules that further damage DNA and cellular components. This oxidative stress compounds the initial DNA damage and can trigger pathways that promote inflammation and abnormal cell signaling. The bone marrow is particularly sensitive to radiation because it contains rapidly dividing cells, which are more vulnerable to DNA damage during replication.
The process often involves activation of cellular stress response pathways, such as the ATM/ATR-p53 pathway, which normally helps repair DNA or induce cell death if the damage is too severe. However, radiation can overwhelm these systems or cause mutations in these very pathways, allowing damaged cells to survive and proliferate abnormally. This can lead to leukopenia initially (a decrease in white blood cells), followed by the emergence of leukemic cells that dominate the bone marrow and bloodstream.
Different types of leukemia vary in their sensitivity to radiation, and factors such as the dose of radiation, the age at exposure, and genetic predispositions influence the risk. For example, children exposed to radiation have a higher risk because their cells are dividing more rapidly, and their DNA repair mechanisms may be less mature. Additionally, inherited deficiencies in DNA repair genes can increase susceptibility to radiation-induced leukemia.
Radiation-induced leukemia was notably observed in survivors of atomic bombings and nuclear accidents, where high doses of radiation caused widespread DNA damage in bone marrow cells. The latency period between exposure and leukemia development can vary from a few years to over a decade, reflecting the time needed for mutations to accumulate and for abnormal cells to expand.
In summary, leukemia is linked to radiation exposure primarily because radiation causes DNA damage in the bone marrow’s blood-forming cells, leading to mutations that disrupt normal cell regulation and promote the development of cancerous white blood cells. The bone marrow’s high radiosensitivity, the generation of reactive oxygen species, and the complex cellular responses to DNA damage all contribute to this increased risk.