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Surgical Rejuvenation of the Ageing Face
Published in John C Watkinson, Raymond W Clarke, Terry M Jones, Vinidh Paleri, Nicholas White, Tim Woolford, Head & Neck Surgery Plastic Surgery, 2018
Gregory S. Dibelius, John M. Hilinski, Dean M. Toriumi
Extrinsic mechanisms of ageing most commonly involve skin damage sustained from solar exposure, known as photoageing. Ultraviolet radiation is well known to contribute to actinic damage through direct or indirect DNA damage. Whereas intrinsic ageing of the skin uniformly results in atrophy of the tissue, actinic changes tend to lead to thickening. In addition, photoageing causes disorganization of dermal elastic tissue fibres, termed elastosis, which contributes to further development of fine skin wrinkles and is a hallmark of the photoageing process.23
Light-Ion Beam Dosimetry
Published in Ben Mijnheer, Clinical 3D Dosimetry in Modern Radiation Therapy, 2017
It is assumed that the distribution of energy deposition on the microscale affects the indirect DNA damage inflicted by radiation via diffusion of radiation-induced reactive species. Microdosimetry concerns the determination of the spatial and temporal distribution of interactions of ionizing radiation within micrometer-sized volumes of matter. The energy dependence of the radiobiological effectiveness (RBE) of light-ions can be related to the variation of the microdosimetric properties. When ionization clustering in the vicinity or within the DNA becomes very high, the diffusion and long-term chemistry (on a time scale longer than 10−7 s) of reactive species becomes less important, and substantial DNA damage will be more directly correlated with the cluster density distribution. This is especially important for heavier ions while for protons and very light-ions the occurrence of such high cluster densities is mainly restricted to the distal edge of the Bragg peak. The measurement or simulation of the clustering distributions within the track structure on the nanoscale is the subject of nanodosimetry. The characterization of track structure is based on the stochastic quantity, called ionization cluster size, and its frequency distribution (ionization cluster size distribution [ICSD]).
The melanocyte and melaninogenesis
Published in Dimitris Rigopoulos, Alexander C. Katoulis, Hyperpigmentation, 2017
Dimitrios Xekardakis, Sabine Krueger-Krasagakis, Konstantinos Krasagakis
UVR affects melaninogenesis both directly and indirectly. UV exposure can cause direct DNA damage in keratinocytes, which is the key step for triggering melaninogenesis, followed by the activation of p53. p53 is a tumor suppressor protein playing a central role in melaninogenesis. After its activation, p53 increases the level of tyrosinase and the release of α-MSH.9,25 UVA causes indirect DNA damage by inducing ROS, whereas UVB acts directly and induces structural DNA damage by forming DNA photoproducts, mainly thymine dimers and pyrimidine(6–4)pyrimidone.15,27 DNA damage occurring immediately after an exposure to UVR is more prolonged, and DNA starts repairing shortly after this.7 All these mechanisms stimulate melaninogenesis in a direct manner, by increasing the proliferation of melanocytes, the transfer of melanosomes, the number of dendrites, and the level of melanogenic enzymes.28 An indirect mode of stimulation of melaninogenesis by UVR constitutes the induction of paracrine factor production by epidermal cells acting on neighboring melanocytes.
Track to the future: historical perspective on the importance of radiation track structure and DNA as a radiobiological target
Published in International Journal of Radiation Biology, 2018
Radiation induced DNA damage is produced either by direct ionization of its constituent atoms or indirectly through reactions with free radicals produced as a result of interactions in the surrounding water. Indirect DNA damage is dominated by hydroxyl radicals (•OH) which are capable of producing either DNA base damage or strand breaks, however, the highly reactive environment within the cell limits their lifetime and therefore their diffusion distance to ∼6 nm (Roots and Okada 1975) thus restricting sites of damage to within a few nanometers of the path of the initiating radiation track. The passage of a single radiation track and the associated pattern of energy deposition events if it intersects with DNA (or passes within a few nanometers) can lead to a wide variety of molecular damage, including base damage, abasic sites, SSB and DNA-protein cross links. However, because ionizing radiation produces multiple energy deposition sites along the radiation track (correlated in time and space), it will frequently produce clustered damage sites, which consist of two or more lesions formed within one or two helical turns of DNA. A wide spectrum of clustered lesions, including DSB can be produced by a single radiation track. The spectrum of damage produced is critically dependent on radiation quality and this has been investigated over the years using Monte Carlo simulation of radiation tracks and modeling of the consequent DNA damage.
Track-structure simulations of energy deposition patterns to mitochondria and damage to their DNA
Published in International Journal of Radiation Biology, 2019
Werner Friedland, Elke Schmitt, Pavel Kundrát, Giorgio Baiocco, Andrea Ottolenghi
DNA damage to nuclear DNA and chromatin is scored in biophysical simulations by overlapping the track structures of photons, electrons, protons or heavier ions with sophisticated multi-scale models of the target structures. Direct damage results from energy depositions in the volume of DNA. Energy depositions outside DNA are processed via pre-chemical and chemical modules of the code, which simulate the formation of radicals from water radiolysis, as well as their diffusion and mutual reactions. Attacks of the radicals onto DNA are scored as indirect DNA damage. Details on model assumptions and parameters such as energy needed to induce a strand break in DNA double helix or the incorporated radical reactions can be found in (Friedland et al. 2011; Friedland and Kundrát 2014).
Approaches for the setting of occupational exposure limits (OELs) for carcinogens
Published in Critical Reviews in Toxicology, 2023
At high doses, sometimes even at the PoD, the direct genotoxic effect of a non-threshold carcinogen is likely amplified by threshold effects such as inflammation and cell death that cause additional, indirect DNA damage or adversely affect DNA repair (Balkwill et al. 2005; Alexandrov et al. 2016; Shi et al. 2017; Benesch et al. 2018; Golemis et al. 2018). Thus, the LNT procedure has a tendency to overestimate the risk at low doses in two ways: (1) by assuming no threshold, implying a risk at doses very close to zero and (2) by neglecting that MoAs that contribute to the response seen at the relatively high doses (from which the PoD is sometimes derived) might be ineffective at low doses. For further discussions of these issues, see Hartwig et al. (2020).