Page 288 - 2014 Printable Abstract Book
P. 288
PS5 PHYSICO-CHEMICAL, TRACK STRUCTURE AND MODELING, TRANSLATIONAL RESEARCH
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(PS5-01) Chemical radiosensitivity of DNA induced by gold nanoparticles. Yi Zheng ; Shiliang Chen ;
1
2
1
Yunfeng Chen ; and Leon Sanche , Fuzhou University, Fuzhou, China and Dept. Nuclear Medicine &
Radiobiology, Univ. of Sherbrooke, Sherbrooke, Canada
2
The potential use of gold nanoparticles (GNPs) as radiosensitizers in cancer radiotherapy has
attracted considerable interest. [1, 2] Essentially, GNPs sensitize biomolecules to radiation in two ways: by
locally increasing the radiation energy absorbed (physical) and by modifying the sensitivity of the target
biomolecules to radiation (chemical). The latter perspective does not appear to have been independently
investigated in the case of GNPs. This lack of information may be due to the difficulty in separating one
mechanism from the other. Taking DNA films as the biological target, we present the first investigation of
the chemical mechanism of radiosensitization by irradiating thin films made of GNP-DNA complexes with
essentially non-ionizing 10-eV electrons. Naked GNPs of 5 and 15 nm diameters were synthesized and
electrostatically bound to DNA. Damage to pure DNA and the GNP-DNA complexes were analyzed, as a
function of electron fluence, by electrophoresis. In identical 5-monolayer films, the yields of DNA damage,
as well as the enhancement factor due to the presence of 5 nm positively-charged nanoparticles,
increased with rising ratio of GNPs to DNA up to 1:1. In comparison, increasing the ratio of negatively-
charged 15 nm GNPs to DNA did not increase damage. As verified by XPS and zeta potential
measurements, the binding of plasmid DNA to the surface of the two sizes of GNPs varies owing to the
characteristics of the GNP surface and electrostatic interaction. The results indicate that strong binding of
GNPs to DNA could significantly influence the efficiency of the chemical radiosensitization mechanism.
This mechanism appears to be an important component of the overall process of GNP radiosensitization
and should be considered when modeling this phenomenon. Our results suggest that small size GNPs
(diam. ~5 nm) are more efficient radiosensitizers compared to larger GNPs when delivered into cancerous
cells, where their action should be cell-cycle dependent. Financial support for this work was provided by
the National Basic Research Program of China (973 Program: 2013CB632405) and the Canadian Institutes
of Health Research (MOP81356). References: [1] S. Jain, et al.2011British J. Radiology,
doi:10.1259/bjr/59448833. [2]S. J. McMahon, et al. 2011 NatureScientific Reports 1, 18.
(PS5-02) Sequence dependence of telomeric and non-telomeric DNA oligomers to prompt strand break
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1
formation from direct-type radiation damage. Paul J. Black, PhD ; Adam Miller, PhD ; and Jeffrey Hayes,
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3
2
PhD ; Wake Forest University, Winston-Salem, NC ; Yale University, New Haven, CT ; and University of
Rochester, Rochester, NY
3
Ionizing radiation from natural, man-made and cosmic sources damages DNA, leading to
deleterious effects, including cancer. Damage is caused both by direct deposition of energy to the DNA
and indirect mechanisms involving ionization of bulk solvent. While indirect damage mechanisms have
been well characterized, mechanisms leading to DNA strand breaks from direct-type damage are still
under investigation. In this work we introduce a method to monitor strand breaks resulting from direct-
type damage and provide evidence for sequence-dependent effects leading to strand breaks. Specifically
we find that direct damage primarily results in a reduced number of strand breaks in guanine triplet
regions when compared to isolated guanine bases with identical flanking base context. In addition, we
286 | P a g e
1
1
(PS5-01) Chemical radiosensitivity of DNA induced by gold nanoparticles. Yi Zheng ; Shiliang Chen ;
1
2
1
Yunfeng Chen ; and Leon Sanche , Fuzhou University, Fuzhou, China and Dept. Nuclear Medicine &
Radiobiology, Univ. of Sherbrooke, Sherbrooke, Canada
2
The potential use of gold nanoparticles (GNPs) as radiosensitizers in cancer radiotherapy has
attracted considerable interest. [1, 2] Essentially, GNPs sensitize biomolecules to radiation in two ways: by
locally increasing the radiation energy absorbed (physical) and by modifying the sensitivity of the target
biomolecules to radiation (chemical). The latter perspective does not appear to have been independently
investigated in the case of GNPs. This lack of information may be due to the difficulty in separating one
mechanism from the other. Taking DNA films as the biological target, we present the first investigation of
the chemical mechanism of radiosensitization by irradiating thin films made of GNP-DNA complexes with
essentially non-ionizing 10-eV electrons. Naked GNPs of 5 and 15 nm diameters were synthesized and
electrostatically bound to DNA. Damage to pure DNA and the GNP-DNA complexes were analyzed, as a
function of electron fluence, by electrophoresis. In identical 5-monolayer films, the yields of DNA damage,
as well as the enhancement factor due to the presence of 5 nm positively-charged nanoparticles,
increased with rising ratio of GNPs to DNA up to 1:1. In comparison, increasing the ratio of negatively-
charged 15 nm GNPs to DNA did not increase damage. As verified by XPS and zeta potential
measurements, the binding of plasmid DNA to the surface of the two sizes of GNPs varies owing to the
characteristics of the GNP surface and electrostatic interaction. The results indicate that strong binding of
GNPs to DNA could significantly influence the efficiency of the chemical radiosensitization mechanism.
This mechanism appears to be an important component of the overall process of GNP radiosensitization
and should be considered when modeling this phenomenon. Our results suggest that small size GNPs
(diam. ~5 nm) are more efficient radiosensitizers compared to larger GNPs when delivered into cancerous
cells, where their action should be cell-cycle dependent. Financial support for this work was provided by
the National Basic Research Program of China (973 Program: 2013CB632405) and the Canadian Institutes
of Health Research (MOP81356). References: [1] S. Jain, et al.2011British J. Radiology,
doi:10.1259/bjr/59448833. [2]S. J. McMahon, et al. 2011 NatureScientific Reports 1, 18.
(PS5-02) Sequence dependence of telomeric and non-telomeric DNA oligomers to prompt strand break
2
1
formation from direct-type radiation damage. Paul J. Black, PhD ; Adam Miller, PhD ; and Jeffrey Hayes,
1
3
2
PhD ; Wake Forest University, Winston-Salem, NC ; Yale University, New Haven, CT ; and University of
Rochester, Rochester, NY
3
Ionizing radiation from natural, man-made and cosmic sources damages DNA, leading to
deleterious effects, including cancer. Damage is caused both by direct deposition of energy to the DNA
and indirect mechanisms involving ionization of bulk solvent. While indirect damage mechanisms have
been well characterized, mechanisms leading to DNA strand breaks from direct-type damage are still
under investigation. In this work we introduce a method to monitor strand breaks resulting from direct-
type damage and provide evidence for sequence-dependent effects leading to strand breaks. Specifically
we find that direct damage primarily results in a reduced number of strand breaks in guanine triplet
regions when compared to isolated guanine bases with identical flanking base context. In addition, we
286 | P a g e
