Heavy charged particle radiobiology: Using enhanced biological effectiveness and improved beam focusing to advance cancer therapy

Department of Environmental and Radiological Health Sciences, Colorado State University, Ft. Collins, CO 80523, USA.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis (Impact Factor: 3.68). 03/2011; 711(1-2):150-7. DOI: 10.1016/j.mrfmmm.2011.02.012
Source: PubMed


Ionizing radiation causes many types of DNA damage, including base damage and single- and double-strand breaks. Photons, including X-rays and γ-rays, are the most widely used type of ionizing radiation in radiobiology experiments, and in radiation cancer therapy. Charged particles, including protons and carbon ions, are seeing increased use as an alternative therapeutic modality. Although the facilities needed to produce high energy charged particle beams are more costly than photon facilities, particle therapy has shown improved cancer survival rates, reflecting more highly focused dose distributions and more severe DNA damage to tumor cells. Despite early successes of charged particle radiotherapy, there is room for further improvement, and much remains to be learned about normal and cancer cell responses to charged particle radiation.

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Available from: Jac Nickoloff, Nov 13, 2014
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    • "The particle beam energy distribution is somewhat different than X-rays and photon beams. The particle beam penetrates deep inside the body (penetration depth depends upon the energy of the beam), at particular depths they give off about 99% of their total energy and then extinguish [7]. This feature is very helpful in targeting the infected tissues without affecting the healthy ones. "
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    ABSTRACT: Mg2BO3F:Dy phosphor is a low Z material with an effective atomic number 9.92. This phosphor was synthesized by two different methods, because the solid state method failed to produce single phase Mg2BO3F:Dy phosphor. This study reports a comparative investigation of γ-ray and C5+ ion beam impact on thermoluminescence (TL) properties of Mg2BO3F:Dy phosphor. TRIM/SRIM calculations were performed to correlate the changes in TL properties of Mg2BO3F:Dy phosphor. Phosphor possesses good TL response towards γ-rays as well as C5+ ion beam irradiation. TL glow curves of the C5+ ion irradiated phosphor show a small shift in the position of the glow peaks towards the lower temperature side. With an increase in energy of the ion beam increase in TL intensity was observed. This increase in the TL efficiency with a decrease in linear energy transfer (LET) agrees well with the results reported in literature. Trapping parameters of the γ-ray and C5+ ion beam irradiated phosphor were calculated from the TL data using computerized glow curve deconvolution method. The trapping analysis suggests that ion beam irradiation causes only minor changes in the activation energy. The different types of defects responsible for TL glow curves were identified using the EPR technique.
    Materials Chemistry and Physics 05/2015; 161. DOI:10.1016/j.matchemphys.2015.05.020 · 2.26 Impact Factor
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    • "Interestingly, these cells showed differential responses to genotoxic stress induced by photon (X-ray) irradiation or particle ion beams. Compared to photons, carbon ion beams deliver a larger mean energy per unit length of their trajectory [8] [9]. The relative biological effectiveness of carbon ion beams with respect to reference photon radiation is estimated to be approximately 2–3-fold, as assessed by biological endpoints such as cell death, DNA damage, and chromosomal aberrations, among others. "
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    • "This is why X-rays and γ-rays are considered sparsely ionizing, or low-linear energy transfer (LET), forms of IR. On the other hand, particulate forms of ionizing radiation such as neutrons, α particles, or carbon ions, are considered densely ionizing, or high LET, forms of radiation because they ionize along their tracks at a higher rate than the electrons generated by X-rays (64). "
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    ABSTRACT: Although the DNA double-strand break (DSB) is defined as a rupture in the double-stranded DNA molecule that can occur without chemical modification in any of the constituent building blocks, it is recognized that this form is restricted to enzyme-induced DSBs. DSBs generated by physical or chemical agents can include at the break site a spectrum of base alterations (lesions). The nature and number of such chemical alterations define the complexity of the DSB and are considered putative determinants for repair pathway choice and the probability that errors will occur during this processing. As the pathways engaged in DSB processing show distinct and frequently inherent propensities for errors, pathway choice also defines the error-levels cells opt to accept. Here, we present a classification of DSBs on the basis of increasing complexity and discuss how complexity may affect processing, as well as how it may cause lethal or carcinogenic processing errors. By critically analyzing the characteristics of DSB repair pathways, we suggest that all repair pathways can in principle remove lesions clustering at the DSB but are likely to fail when they encounter clusters of DSBs that cause a local form of chromothripsis. In the same framework, we also analyze the rational of DSB repair pathway choice.
    Nucleic Acids Research 06/2013; 41(16). DOI:10.1093/nar/gkt556 · 9.11 Impact Factor
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