Limits...
Shorter exposures to harder X-rays trigger early apoptotic events in Xenopus laevis embryos.

Dong J, Mury SP, Drahos KE, Moscovitch M, Zia RK, Finkielstein CV - PLoS ONE (2010)

Bottom Line: Our research challenges the current dogma of dose-dependent induction of apoptosis and establishes a new parallel paradigm to the photoelectric effect in biological systems.Overall, our data establish that the energy of the incident photon is a major contributor to the outcome of the biological system.These results suggest that biological organisms display properties similar to the photoelectric effect in physical systems and provide new insights into how radiation-mediated apoptosis should be understood and utilized for therapeutic purposes.

View Article: PubMed Central - PubMed

Affiliation: Department of Physics, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America.

ABSTRACT

Background: A long-standing conventional view of radiation-induced apoptosis is that increased exposure results in augmented apoptosis in a biological system, with a threshold below which radiation doses do not cause any significant increase in cell death. The consequences of this belief impact the extent to which malignant diseases and non-malignant conditions are therapeutically treated and how radiation is used in combination with other therapies. Our research challenges the current dogma of dose-dependent induction of apoptosis and establishes a new parallel paradigm to the photoelectric effect in biological systems.

Methodology/principal findings: We explored how the energy of individual X-ray photons and exposure time, both factors that determine the total dose, influence the occurrence of cell death in early Xenopus embryo. Three different experimental scenarios were analyzed and morphological and biochemical hallmarks of apoptosis were evaluated. Initially, we examined cell death events in embryos exposed to increasing incident energies when the exposure time was preset. Then, we evaluated the embryo's response when the exposure time was augmented while the energy value remained constant. Lastly, we studied the incidence of apoptosis in embryos exposed to an equal total dose of radiation that resulted from increasing the incoming energy while lowering the exposure time.

Conclusions/significance: Overall, our data establish that the energy of the incident photon is a major contributor to the outcome of the biological system. In particular, for embryos exposed under identical conditions and delivered the same absorbed dose of radiation, the response is significantly increased when shorter bursts of more energetic photons are used. These results suggest that biological organisms display properties similar to the photoelectric effect in physical systems and provide new insights into how radiation-mediated apoptosis should be understood and utilized for therapeutic purposes.

Show MeSH

Related in: MedlinePlus

Xenopus embryos exhibit different biological responses to the same dose of radiation.A. Embryos irradiated (γ-IR) or not (control) before the MBT were collected at the indicated energies and times as summarized in Fig. S2.C. Caspase activity was assayed as described in the legend of Figure 2. Points indicate the average of ten embryos at each time stage. Figure shows data from a single experiment that was repeated three times with similar results. B. Morphology of Xenopus embryos non-irradiated (control) or irradiated with 20 kV for 60 min and collected at MBT (st.8), st.8+8 h and st.8+16 h. For comparison, an embryo treated with 60 kV for 10 min and collected at st.8+16 h is displayed. Inset shows a higher magnification image of typical apoptotic morphology from a similar embryo. C. Morphology of Xenopus embryos non-irradiated (control) or irradiated with 30, 40, 50, 60 kV for 20, 15, 12 and 10 min, respectively, and collected 8 h after the MBT. Scale bar, 250 µm. D. Caspases 3/7 activity were also assessed by cleavage of the radiolabeled cyclin A2 in extracts from control (non-irradiated) or γ-IR with the same total dose as indicated. Arrows on the right denote radiolabeled Xenopus cyclin A2 (XA2) and its cleaved form.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2813296&req=5

pone-0008970-g005: Xenopus embryos exhibit different biological responses to the same dose of radiation.A. Embryos irradiated (γ-IR) or not (control) before the MBT were collected at the indicated energies and times as summarized in Fig. S2.C. Caspase activity was assayed as described in the legend of Figure 2. Points indicate the average of ten embryos at each time stage. Figure shows data from a single experiment that was repeated three times with similar results. B. Morphology of Xenopus embryos non-irradiated (control) or irradiated with 20 kV for 60 min and collected at MBT (st.8), st.8+8 h and st.8+16 h. For comparison, an embryo treated with 60 kV for 10 min and collected at st.8+16 h is displayed. Inset shows a higher magnification image of typical apoptotic morphology from a similar embryo. C. Morphology of Xenopus embryos non-irradiated (control) or irradiated with 30, 40, 50, 60 kV for 20, 15, 12 and 10 min, respectively, and collected 8 h after the MBT. Scale bar, 250 µm. D. Caspases 3/7 activity were also assessed by cleavage of the radiolabeled cyclin A2 in extracts from control (non-irradiated) or γ-IR with the same total dose as indicated. Arrows on the right denote radiolabeled Xenopus cyclin A2 (XA2) and its cleaved form.

Mentions: We then look at the effect of radiation on the embryos' fate from a different perspective and ask whether their biological response depends exclusively on the total dose administered to the system. To test this possibility directly, we delivered the same total dose to embryos using different photon energies and exposure times (Fig. 5). Specifically, we irradiated embryos with energies equal to 20, 30, 40, 50 and 60 kV for 60, 20, 15, 12, and 10 min, respectively. In each case, dose values were determined by microdosimetry using the appropriate calibration of the instrument (Fig. S2.B) as described in the Materials and Methods section. A summary of the experimental dose values for each kVxmin combination is presented in Fig. S2.C. In all cases, the absorbed dose was of 82.45 Gy±8.4 and therefore comparable (Fig. S2.C).


Shorter exposures to harder X-rays trigger early apoptotic events in Xenopus laevis embryos.

Dong J, Mury SP, Drahos KE, Moscovitch M, Zia RK, Finkielstein CV - PLoS ONE (2010)

Xenopus embryos exhibit different biological responses to the same dose of radiation.A. Embryos irradiated (γ-IR) or not (control) before the MBT were collected at the indicated energies and times as summarized in Fig. S2.C. Caspase activity was assayed as described in the legend of Figure 2. Points indicate the average of ten embryos at each time stage. Figure shows data from a single experiment that was repeated three times with similar results. B. Morphology of Xenopus embryos non-irradiated (control) or irradiated with 20 kV for 60 min and collected at MBT (st.8), st.8+8 h and st.8+16 h. For comparison, an embryo treated with 60 kV for 10 min and collected at st.8+16 h is displayed. Inset shows a higher magnification image of typical apoptotic morphology from a similar embryo. C. Morphology of Xenopus embryos non-irradiated (control) or irradiated with 30, 40, 50, 60 kV for 20, 15, 12 and 10 min, respectively, and collected 8 h after the MBT. Scale bar, 250 µm. D. Caspases 3/7 activity were also assessed by cleavage of the radiolabeled cyclin A2 in extracts from control (non-irradiated) or γ-IR with the same total dose as indicated. Arrows on the right denote radiolabeled Xenopus cyclin A2 (XA2) and its cleaved form.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2813296&req=5

pone-0008970-g005: Xenopus embryos exhibit different biological responses to the same dose of radiation.A. Embryos irradiated (γ-IR) or not (control) before the MBT were collected at the indicated energies and times as summarized in Fig. S2.C. Caspase activity was assayed as described in the legend of Figure 2. Points indicate the average of ten embryos at each time stage. Figure shows data from a single experiment that was repeated three times with similar results. B. Morphology of Xenopus embryos non-irradiated (control) or irradiated with 20 kV for 60 min and collected at MBT (st.8), st.8+8 h and st.8+16 h. For comparison, an embryo treated with 60 kV for 10 min and collected at st.8+16 h is displayed. Inset shows a higher magnification image of typical apoptotic morphology from a similar embryo. C. Morphology of Xenopus embryos non-irradiated (control) or irradiated with 30, 40, 50, 60 kV for 20, 15, 12 and 10 min, respectively, and collected 8 h after the MBT. Scale bar, 250 µm. D. Caspases 3/7 activity were also assessed by cleavage of the radiolabeled cyclin A2 in extracts from control (non-irradiated) or γ-IR with the same total dose as indicated. Arrows on the right denote radiolabeled Xenopus cyclin A2 (XA2) and its cleaved form.
Mentions: We then look at the effect of radiation on the embryos' fate from a different perspective and ask whether their biological response depends exclusively on the total dose administered to the system. To test this possibility directly, we delivered the same total dose to embryos using different photon energies and exposure times (Fig. 5). Specifically, we irradiated embryos with energies equal to 20, 30, 40, 50 and 60 kV for 60, 20, 15, 12, and 10 min, respectively. In each case, dose values were determined by microdosimetry using the appropriate calibration of the instrument (Fig. S2.B) as described in the Materials and Methods section. A summary of the experimental dose values for each kVxmin combination is presented in Fig. S2.C. In all cases, the absorbed dose was of 82.45 Gy±8.4 and therefore comparable (Fig. S2.C).

Bottom Line: Our research challenges the current dogma of dose-dependent induction of apoptosis and establishes a new parallel paradigm to the photoelectric effect in biological systems.Overall, our data establish that the energy of the incident photon is a major contributor to the outcome of the biological system.These results suggest that biological organisms display properties similar to the photoelectric effect in physical systems and provide new insights into how radiation-mediated apoptosis should be understood and utilized for therapeutic purposes.

View Article: PubMed Central - PubMed

Affiliation: Department of Physics, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America.

ABSTRACT

Background: A long-standing conventional view of radiation-induced apoptosis is that increased exposure results in augmented apoptosis in a biological system, with a threshold below which radiation doses do not cause any significant increase in cell death. The consequences of this belief impact the extent to which malignant diseases and non-malignant conditions are therapeutically treated and how radiation is used in combination with other therapies. Our research challenges the current dogma of dose-dependent induction of apoptosis and establishes a new parallel paradigm to the photoelectric effect in biological systems.

Methodology/principal findings: We explored how the energy of individual X-ray photons and exposure time, both factors that determine the total dose, influence the occurrence of cell death in early Xenopus embryo. Three different experimental scenarios were analyzed and morphological and biochemical hallmarks of apoptosis were evaluated. Initially, we examined cell death events in embryos exposed to increasing incident energies when the exposure time was preset. Then, we evaluated the embryo's response when the exposure time was augmented while the energy value remained constant. Lastly, we studied the incidence of apoptosis in embryos exposed to an equal total dose of radiation that resulted from increasing the incoming energy while lowering the exposure time.

Conclusions/significance: Overall, our data establish that the energy of the incident photon is a major contributor to the outcome of the biological system. In particular, for embryos exposed under identical conditions and delivered the same absorbed dose of radiation, the response is significantly increased when shorter bursts of more energetic photons are used. These results suggest that biological organisms display properties similar to the photoelectric effect in physical systems and provide new insights into how radiation-mediated apoptosis should be understood and utilized for therapeutic purposes.

Show MeSH
Related in: MedlinePlus