Reactive oxygen species (ROS) are responsible for biological damage in many pathologic processes and in therapy to eradicate diseased tissue. Although ROS tend to be considered as a common group there is substantial variation in the chemical properties of different ROS, which can have a great influence on their reaction mechanism in a cellular environment. The consequences of ROS production in cells also depend on reactive targets in the vicinity of the ROS. Highly reactive ROS will therefore generate localized primary damage while less reactive ROS have the ability to diffuse further before oxidative reaction occurs. The situation is further complicated as primary reactions can lead to different secondary ROS that have their own particular reactivity and range of reaction and may themselves, impart significant biological responses in cells. The overall goals of this project are to understand the reactivity of primary ROS as a function of the nature of the ROS and site of reaction and to ascertain the potential roles of secondary ROS in exacerbating oxidative damage mechanisms. The project has three specific aims. (1) Test the hypothesis that the level of primary oxidative damage to cells is dependent on the reactivity of the reactive oxygen species (ROS) produced and its location in cells. (2) Test the hypothesis that the inherent reactivity of a ROS will determine the range to which its direct effects can be exerted but that secondary ROS may have a powerful influence on biological responses. (3) Test the hypothesis that photosensitized lipid peroxidation can be a key initiator for DNA damage and in induction of the bystander effect in photosensitization. The information produced in these studies will provide a better understanding of the roles and interaction between ROS in cells and a quantitative understanding of sub-cellular targeting of ROS that can be harnessed to improve efficacy and safety of therapeutic approaches that are based on oxidative damage.
| Prise, K M; Schettino, G (2011) Microbeams in radiation biology: review and critical comparison. Radiat Prot Dosimetry 143:335-9 |
| Purschke, Martin; Rubio, Noemi; Held, Kathryn D et al. (2010) Phototoxicity of Hoechst 33342 in time-lapse fluorescence microscopy. Photochem Photobiol Sci 9:1634-9 |
| Schettino, Giuseppe; Al Rashid, Shahnaz T; Prise, Kevin M (2010) Radiation microbeams as spatial and temporal probes of subcellular and tissue response. Mutat Res 704:68-77 |
| Prise, Kevin M; Schettino, Giuseppe; Vojnovic, Boris et al. (2009) Microbeam studies of the bystander response. J Radiat Res 50 Suppl A:A1-6 |
| Rubio, Noemi; Fleury, Sean P; Redmond, Robert W (2009) Spatial and temporal dynamics of in vitro photodynamic cell killing: extracellular hydrogen peroxide mediates neighbouring cell death. Photochem Photobiol Sci 8:457-64 |
| Zhang, Ying; Zhou, Junqing; Baldwin, Joseph et al. (2009) Ionizing radiation-induced bystander mutagenesis and adaptation: quantitative and temporal aspects. Mutat Res 671:20-5 |
| Prise, Kevin M; O'Sullivan, Joe M (2009) Radiation-induced bystander signalling in cancer therapy. Nat Rev Cancer 9:351-60 |
| Burdak-Rothkamm, Susanne; Prise, Kevin M (2009) New molecular targets in radiotherapy: DNA damage signalling and repair in targeted and non-targeted cells. Eur J Pharmacol 625:151-5 |
| Rubio, Noemi; Rajadurai, Anpuchchelvi; Held, Kathryn D et al. (2009) Real-time imaging of novel spatial and temporal responses to photodynamic stress. Free Radic Biol Med 47:283-90 |
| Chakraborty, Asima; Held, Kathryn D; Prise, Kevin M et al. (2009) Bystander effects induced by diffusing mediators after photodynamic stress. Radiat Res 172:74-81 |
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