Free Radicals

Free radicals have a high degree of chemical reactivity.^4,10 When they interact with cellular macromolecules, e.g., proteins, and alter their chemical structures, they cause repairable or non-repairable damage with significant downstream effects such as altered cell function or cell death.^5,6,8 The effect of free radicals on deoxyribonucleic acid (DNA), which contains the genetic code, is the most important and varies during the various phases of the cell cycle.^{2,4‑6,8,11,12}

Normal cells go through five physiological phases: G0, G1, S, G2, and M (Figure 2).¹³ The G0 phase is the latent or resting phase. Cells recruited from the G0 phase enter the G1 or the first active phase of the reproductive cycle. In the G1 phase, the cells synthesize ribonucleic acid (RNA), enzymes, and proteins in anticipation of entering subsequent phases of the reproductive cycle.

Figure 2. Five physiological phases of the cell cycle: G0, G1, S, G2, and M.

Figure 2. Five physiological phases of the cell cycle: G0, G1, S, G2, and M.

The S phase follows the G1 phase. The predominant event in the S phase is the synthesis of DNA. At the end of the S phase, the cells contain twice the original amount of DNA. The G2 phase follows the S phase. During the G2 phase, the mitotic spindle is created, which is essential for cell divisionIn the M or mitotic phase, cell division occurs. Cells are most radiosensitive in the G1, G2, and M phases, respectively. During the S phase, the cells are the most radioresistant. (Figure 3).^8,11

Figure 3. Cells are most radiosensitive in the G1, G2, and M phases, respectively; and most radioresistant in the S phase.

Figure 3. Cells are most radiosensitive in the G1, G2, and M phases, respectively; and most radioresistant in the S phase.

There is a wide variation in radiosensitivity among different cell types. For example, rapidly dividing cells or cells with a potential for rapid division are more radiosensitive than those that do not divide. In addition, undifferentiated cells are more radiosensitive than highly specialized cells. Finally, within the same cell families, the immature forms rapidly dividing are more radiosensitive than the mature cells that have specialized in function and have ceased to divide.^6,8,10

In summary, cell radiosensitivity is directly proportional to the rate of cell division and inversely proportional to the degree of cell differentiation, i.e., actively dividing cells or those not fully mature are most at risk from radiation. Highly sensitive cells include germ cells, immature red blood cells, and lymphocytes (an exception to the above). Epithelial cells are moderate to highly radiosensitive. Cells of low radiosensitivity include muscle and nerve.