Comprehensive Physiology Wiley Online Library

Effects of Ionizing Radiation on Mammalian Cells

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Abstract

The sections in this article are:

1 Physical and Chemical Events
1.1 Development of Radiation Injury
1.2 The Target Theory
1.3 Direct and Indirect Effects, Radiation Chemistry
2 Effects on Cell Division
2.1 Division Delay
2.2 Mitotic Inhibition (Reproductive Failure)
2.3 Radiation Sensitivity in Different Phases of the Life Cycle
2.4 Chromosomal Damage
2.5 Interphase Death
2.6 Nonlethal Heritable Changes
2.7 Biological Variation in Radiation Sensitivity
2.8 Mechanisms
3 Modification of Radiation Effects
3.1 Physical Factors
3.2 Chemical Radiation Protection and Sensitization
3.3 Oxygen Effect
3.4 Intracellular Recovery Processes
3.5 Repair of Potentially Lethal Damage
3.6 Repair of Sublethal Damage (Split‐Dose Recovery)
4 Molecular Repair Processes
4.1 Damage Observed in DNA
4.2 Cellular Repair Systems for DNA Damage
4.3 Repair Activities in Mammalian Cells
4.4 Correlation of DNA Repair with Biological Effects
5 Concluding Remarks
6 Addendum
Figure 1. Figure 1.

Development of radiation injury in cells.

Figure 2. Figure 2.

Hypothetical dose‐response curves for radiation‐induced reproductive failure in cells. Curve 1 is often referred to as a single‐event and curve 2 a multiple‐event survival curve. The latter is the type associated with the killing of mammalian cells by gamma or X‐irradiation, and its shape can be described by two parameters: the extrapolation number ñ, which indicates the magnitude of the shoulder on the curve, and the D0 or dose necessary to reduce survival to 37% on the linear portion of the curve, which determines its slope. Mathematically the D0 is the inverse of the slope.

Figure 3. Figure 3.

Stages of interphase during life cycle of a typical mammalian cell. DNA synthesis (S phase) occurs during a discrete period when genetic material is reduplicated. The phases before and after S are called G1 and G2 (gaps). The time periods shown for each stage are typical for cells with a 20‐h generation time, although generation time and length of the three stages of interphase vary among different cell types.

Figure 4. Figure 4.

Pedigrees of X‐irradiated mouse L cells obtained by time‐lapse cinematography. Both cells were irradiated with 216 rads. Numbers are generation times in hours. PYK, pyknosis (staining abnormality indicating cell death); arrows, nondividing cells. A: Expression of damage delayed until after the 4th division. Injury manifest primarily in the 6th and 7th divisions in a variety of ways including pyknosis, nondivision, giant cell formation, abnormal mitosis such as fusion and multipolar division, and prolonged generation times. Some progeny will probably survive. B: Abortive clone with extensive cell death in several generations. It is unlikely that any of the progeny survived to proliferate indefinitely.

From Thompson & Suit
Figure 5. Figure 5.

X‐ray survival curves for synchronized cultures of Chinese hamster cells irradiated during various stages of the cell cycle.

From Sinclair & Morton
Figure 6. Figure 6.

Repair of potentially lethal damage in a line of human liver cells (LICH). Cells were irradiated while in the density‐inhibited phase of growth. They were then subcultured to assay for survival either immediately or 6 h later. The enhanced survival found in cells allowed to remain under conditions of growth inhibition for 6 h after a single dose of radiation is due to a change in the slope of the survival curve.

From Little et al.
Figure 7. Figure 7.

Split‐dose recovery in human LICH cells. The curve on the left is the single‐dose survival curve. The shoulder is interpreted as representing the accumulation of sublethal damage by the cells at low radiation doses. The survival curve on the right was obtained with cells that had survived a single dose of 600 rads given 6 h before. The return of the shoulder is interpreted as indicating that the sublethal damage incurred during the first exposure was repaired between doses. Net survival following 1,000 rads, for example, was about three times greater when the dose was split for two fractions. Note there was no change in the slope of the survival curve. PE, plating efficiency; D0, inverse of slope; ñ, extrapolation number.

Figure 8. Figure 8.

Variation of the mean fraction number of the DNA sedimentation peak against minutes of repair incubation at 37°C after 10 kilorads of gamma irradiation. Cells were labeled with tritiated thymidine for 24–50 h, irradiated, placed in repair media at 37°C for specified times, then suspended, lysed, and centrifuged using the technique of McGrath & Williams . On the ordinate, fractions 16–18 would correspond to DNA molecules of 2 to 5 × 108 daltons, fractions 7 −9 would correspond to DNA molecules of 2 to 7 × 107 daltons. ○, diploid fibroblasts from a patient with precocious aging; □, diploid fibroblasts from a normal adult; Δ, diploid fibroblasts from a normal human fetus; ⋄ aneuploid human cells (LICH).

From Epstein et al.
Figure 9. Figure 9.

Alternate rejoining and incision of DNA molecules after gamma irradiation in aneuploid human cells (LICH). Conditions are similar to those described in the legend of Figure .

Figure 10. Figure 10.

Survival of a hybrid cell line αRST (○—○), and its parent cell lines, Cl‐1D (x—x) and GH12Cl (○‐○) after graded doses of X‐radiation.

From Little et al.


Figure 1.

Development of radiation injury in cells.



Figure 2.

Hypothetical dose‐response curves for radiation‐induced reproductive failure in cells. Curve 1 is often referred to as a single‐event and curve 2 a multiple‐event survival curve. The latter is the type associated with the killing of mammalian cells by gamma or X‐irradiation, and its shape can be described by two parameters: the extrapolation number ñ, which indicates the magnitude of the shoulder on the curve, and the D0 or dose necessary to reduce survival to 37% on the linear portion of the curve, which determines its slope. Mathematically the D0 is the inverse of the slope.



Figure 3.

Stages of interphase during life cycle of a typical mammalian cell. DNA synthesis (S phase) occurs during a discrete period when genetic material is reduplicated. The phases before and after S are called G1 and G2 (gaps). The time periods shown for each stage are typical for cells with a 20‐h generation time, although generation time and length of the three stages of interphase vary among different cell types.



Figure 4.

Pedigrees of X‐irradiated mouse L cells obtained by time‐lapse cinematography. Both cells were irradiated with 216 rads. Numbers are generation times in hours. PYK, pyknosis (staining abnormality indicating cell death); arrows, nondividing cells. A: Expression of damage delayed until after the 4th division. Injury manifest primarily in the 6th and 7th divisions in a variety of ways including pyknosis, nondivision, giant cell formation, abnormal mitosis such as fusion and multipolar division, and prolonged generation times. Some progeny will probably survive. B: Abortive clone with extensive cell death in several generations. It is unlikely that any of the progeny survived to proliferate indefinitely.

From Thompson & Suit


Figure 5.

X‐ray survival curves for synchronized cultures of Chinese hamster cells irradiated during various stages of the cell cycle.

From Sinclair & Morton


Figure 6.

Repair of potentially lethal damage in a line of human liver cells (LICH). Cells were irradiated while in the density‐inhibited phase of growth. They were then subcultured to assay for survival either immediately or 6 h later. The enhanced survival found in cells allowed to remain under conditions of growth inhibition for 6 h after a single dose of radiation is due to a change in the slope of the survival curve.

From Little et al.


Figure 7.

Split‐dose recovery in human LICH cells. The curve on the left is the single‐dose survival curve. The shoulder is interpreted as representing the accumulation of sublethal damage by the cells at low radiation doses. The survival curve on the right was obtained with cells that had survived a single dose of 600 rads given 6 h before. The return of the shoulder is interpreted as indicating that the sublethal damage incurred during the first exposure was repaired between doses. Net survival following 1,000 rads, for example, was about three times greater when the dose was split for two fractions. Note there was no change in the slope of the survival curve. PE, plating efficiency; D0, inverse of slope; ñ, extrapolation number.



Figure 8.

Variation of the mean fraction number of the DNA sedimentation peak against minutes of repair incubation at 37°C after 10 kilorads of gamma irradiation. Cells were labeled with tritiated thymidine for 24–50 h, irradiated, placed in repair media at 37°C for specified times, then suspended, lysed, and centrifuged using the technique of McGrath & Williams . On the ordinate, fractions 16–18 would correspond to DNA molecules of 2 to 5 × 108 daltons, fractions 7 −9 would correspond to DNA molecules of 2 to 7 × 107 daltons. ○, diploid fibroblasts from a patient with precocious aging; □, diploid fibroblasts from a normal adult; Δ, diploid fibroblasts from a normal human fetus; ⋄ aneuploid human cells (LICH).

From Epstein et al.


Figure 9.

Alternate rejoining and incision of DNA molecules after gamma irradiation in aneuploid human cells (LICH). Conditions are similar to those described in the legend of Figure .



Figure 10.

Survival of a hybrid cell line αRST (○—○), and its parent cell lines, Cl‐1D (x—x) and GH12Cl (○‐○) after graded doses of X‐radiation.

From Little et al.
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John B. Little, Jerry R. Williams. Effects of Ionizing Radiation on Mammalian Cells. Compr Physiol 2011, Supplement 26: Handbook of Physiology, Reactions to Environmental Agents: 127-155. First published in print 1977. doi: 10.1002/cphy.cp090108