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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.

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Related in: MedlinePlus

High-dose radiation raises caspase activity and favors cyclin A2 cleavage.Extracts equivalent to ten embryos from non-irradiated (control) or irradiated (γ-IR) samples collected at MBT (st.8, A) and 4 h after the MBT (B) were incubated with radiolabeled cyclin A2 as described in the “Materials and Methods” section. Aliquots were removed at the indicated times and analyzed for cyclin A2 cleavage by SDS-PAGE and autoradiography. Control samples correspond to non-irradiated embryos. Arrows on the right denote radiolabeled Xenopus cyclin A2 (XA2) and its cleaved form.
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pone-0008970-g004: High-dose radiation raises caspase activity and favors cyclin A2 cleavage.Extracts equivalent to ten embryos from non-irradiated (control) or irradiated (γ-IR) samples collected at MBT (st.8, A) and 4 h after the MBT (B) were incubated with radiolabeled cyclin A2 as described in the “Materials and Methods” section. Aliquots were removed at the indicated times and analyzed for cyclin A2 cleavage by SDS-PAGE and autoradiography. Control samples correspond to non-irradiated embryos. Arrows on the right denote radiolabeled Xenopus cyclin A2 (XA2) and its cleaved form.

Mentions: Cleavage of radiolabeled cyclin A2 added to extracts also supported caspases 3/7 activation in response to various radiation conditions (Fig. 4). Extracts from embryos irradiated with 20–60 kV for various times were incubated with labeled cyclin A2 and samples were analyzed as described in the Materials and Methods section. We decided to monitor cyclin A2 cleavage in extracts of irradiated embryos obtained from two developmental stages MBT (st.8) and early gastrulation (∼st.8+4 h). We chose these stages because at the MBT, development becomes more complex as transcription initiates, the cell cycle lengthens, and cells differentiate and organize during gastrulation. It is precisely at gastrulation when the embryo takes complete control over cell division. In addition, results presented in Fig. 3 clearly establish that embryos irradiated with doses equal to or greater than 30 kV exhibit caspase activity values above the threshold by 6 h after the MBT; thus, a subtle response to radiation is conspicuous only at early times.


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)

High-dose radiation raises caspase activity and favors cyclin A2 cleavage.Extracts equivalent to ten embryos from non-irradiated (control) or irradiated (γ-IR) samples collected at MBT (st.8, A) and 4 h after the MBT (B) were incubated with radiolabeled cyclin A2 as described in the “Materials and Methods” section. Aliquots were removed at the indicated times and analyzed for cyclin A2 cleavage by SDS-PAGE and autoradiography. Control samples correspond to non-irradiated embryos. 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-g004: High-dose radiation raises caspase activity and favors cyclin A2 cleavage.Extracts equivalent to ten embryos from non-irradiated (control) or irradiated (γ-IR) samples collected at MBT (st.8, A) and 4 h after the MBT (B) were incubated with radiolabeled cyclin A2 as described in the “Materials and Methods” section. Aliquots were removed at the indicated times and analyzed for cyclin A2 cleavage by SDS-PAGE and autoradiography. Control samples correspond to non-irradiated embryos. Arrows on the right denote radiolabeled Xenopus cyclin A2 (XA2) and its cleaved form.
Mentions: Cleavage of radiolabeled cyclin A2 added to extracts also supported caspases 3/7 activation in response to various radiation conditions (Fig. 4). Extracts from embryos irradiated with 20–60 kV for various times were incubated with labeled cyclin A2 and samples were analyzed as described in the Materials and Methods section. We decided to monitor cyclin A2 cleavage in extracts of irradiated embryos obtained from two developmental stages MBT (st.8) and early gastrulation (∼st.8+4 h). We chose these stages because at the MBT, development becomes more complex as transcription initiates, the cell cycle lengthens, and cells differentiate and organize during gastrulation. It is precisely at gastrulation when the embryo takes complete control over cell division. In addition, results presented in Fig. 3 clearly establish that embryos irradiated with doses equal to or greater than 30 kV exhibit caspase activity values above the threshold by 6 h after the MBT; thus, a subtle response to radiation is conspicuous only at early times.

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