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 either repairable or non-repairable damage with important 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 are cycled through five physiological phases: G0, G1, S, G2, and M (Figure 2).¹³ The G0 phase is a latent or resting phase during which the cells are preparing to be recruited into the reproductive cycle. 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.

The G1 phase is followed by the S phase. The predominant event in S phase is the synthesis of DNA. At the end of S phase, the cells contain twice the original amount of DNA. The S phase is followed by the G2 phase during which the mitotic spindle essential for cell division is created. In the M or mitotic phase, cell division occurs. In general, cells are most radiosensitive in the G1, G2, and M phases, respectively; and most radioresistant in the S phase (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.

There is wide variation in radiosensitivity among different cell types. Rapidly dividing cells or cells that have a potential for rapid division are more radiosensitive than cell that do not divide; cells that are undifferentiated are more radiosensitive than those that are highly specialized; finally, within the same cell families, the immature forms, which are 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. Based on these factors highly sensitive cells include germ cells, immature red blood cells, and lymphocytes (an exception to the above); epithelial cells are moderately to highly radiosensitive; and cells of low radiosensitivity include muscle and nerve..

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