What phase of the cell cycle is most affected by radiation?

Radiation Effects on Cell Cycle Phases

The M phase (mitosis) is the most radiosensitive phase of the cell cycle, followed by G2, G1, with late S phase being the most radioresistant. 1

Radiosensitivity Across Cell Cycle Phases

• Cells in M phase (mitosis) and at the G1/S interface demonstrate the highest sensitivity to radiation exposure 2
• G2 phase shows significant radiosensitivity, with cells experiencing pronounced delays and checkpoint activation after radiation 3
• G1 phase demonstrates intermediate sensitivity to radiation 1
• Late S phase is the most radioresistant phase of the cell cycle 1, 4

Mechanisms of Radiation-Induced Cell Cycle Effects

M Phase Sensitivity

• Mitotic cells lack time for DNA damage repair before chromosome segregation, making them particularly vulnerable to radiation effects 1
• The cytoskeletal structure during mitosis and chromosome condensation contribute to increased radiosensitivity 2

G2 Phase Effects

• Radiation induces a prominent G2 checkpoint activation, causing cell cycle arrest 3
• G2 arrest is observed in virtually all eukaryotic cells in response to radiation 4
• Control of radiation-induced G2 delay involves modulation of cyclin B1/p34cdc2 activity 4
• High-LET radiation causes a more profound block in G2 phase than low-LET radiation 2

G1 Phase Effects

• G1 arrest is regulated by the p53 tumor suppressor gene product 4
• Radiation increases p53 expression, which induces WAF1/Cip1 protein that inhibits cyclin-dependent kinases 4
• Normal fibroblasts irradiated in G1 phase may remain permanently arrested after exposure, especially with high-LET radiation 3

S Phase Effects

• S phase demonstrates the greatest radioresistance, particularly in late S phase 1
• Low-LET radiation delays progression through S phase, potentially allowing more time for repair 2
• S phase delay has both radiosensitive and radioresistant components, corresponding to inhibition of DNA replicon initiation and DNA chain elongation 4

Clinical Implications

• Understanding cell cycle radiosensitivity has led to the realization that chemotherapy and fractionated radiotherapy may work better by partially synchronizing cells in the most radiosensitive phases 1
• Mitotically active hematopoietic progenitors have limited capacity to divide after whole-body radiation doses greater than 2-3 Gy 5, 6
• The hematopoietic syndrome from radiation exposure results from damage to actively dividing bone marrow stem and progenitor cells 5, 6
• Radiation-induced pancytopenia predisposes to infection, bleeding, and poor wound healing 6

Cellular Response Mechanisms

• Radiation damage activates cell cycle checkpoints that permit time for genetic repair or trigger irreversible growth arrest 1
• Checkpoint activation involves sensor (RAD, BRCA, NBS1), transducer (ATM, CHK), and effector (p53, p21, CDK) genes 1
• DNA-dependent protein kinase (DNA-PK) activity influences cell cycle checkpoint response, though G2 checkpoint remains intact even in cells lacking DNA-PK activity 7
• High-LET radiation is a more potent inducer of cell cycle delays than low-LET radiation at equivalent doses 3

In summary, the differential sensitivity of cell cycle phases to radiation follows the pattern of M > G2 > G1 > S (late), with mitosis being the most vulnerable phase. This understanding is crucial for optimizing radiation therapy protocols and understanding radiation injury mechanisms.