Induction, repair and biological relevance of radiation-induced DNA lesions in eukaryotic cells

1990 ◽  
Vol 29 (4) ◽  
pp. 273-292 ◽  
Author(s):  
M. Frankenberg-Schwager
2020 ◽  
Vol 21 (21) ◽  
pp. 8151
Author(s):  
Sharda Kumari ◽  
Shibani Mukherjee ◽  
Debapriya Sinha ◽  
Salim Abdisalaam ◽  
Sunil Krishnan ◽  
...  

Radiation therapy (RT), an integral component of curative treatment for many malignancies, can be administered via an increasing array of techniques. In this review, we summarize the properties and application of different types of RT, specifically, conventional therapy with x-rays, stereotactic body RT, and proton and carbon particle therapies. We highlight how low-linear energy transfer (LET) radiation induces simple DNA lesions that are efficiently repaired by cells, whereas high-LET radiation causes complex DNA lesions that are difficult to repair and that ultimately enhance cancer cell killing. Additionally, we discuss the immunogenicity of radiation-induced tumor death, elucidate the molecular mechanisms by which radiation mounts innate and adaptive immune responses and explore strategies by which we can increase the efficacy of these mechanisms. Understanding the mechanisms by which RT modulates immune signaling and the key players involved in modulating the RT-mediated immune response will help to improve therapeutic efficacy and to identify novel immunomodulatory drugs that will benefit cancer patients undergoing targeted RT.


1990 ◽  
Vol 122 (3) ◽  
pp. 316 ◽  
Author(s):  
Helen H. Evans ◽  
Mark Nielsen ◽  
Jaroslav Mencl ◽  
Min-Fen Horng ◽  
Marlene Ricanati

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mario E. Alcocer-Ávila ◽  
Michele A. Quinto ◽  
Juan M. Monti ◽  
Roberto D. Rivarola ◽  
Christophe Champion

Abstract Whether it is in radiobiology to identify DNA lesions or in medicine to adapt the radiotherapeutic protocols, a detailed understanding of the radiation-induced interactions in living matter is required. Monte Carlo track-structure codes have been successfully developed to describe these interactions and predict the radiation-induced energy deposits at the nanoscale level in the medium of interest. In this work, the quantum-mechanically based Monte Carlo track-structure code TILDA-V has been used to compute the slowing-down of protons in water and DNA. Stopping power and range are then reported and compared with existing data. Then, a first application of TILDA-V to cellular irradiations is also reported in order to highlight the absolute necessity of taking into account a realistic description of the cellular environment in microdosimetry.


2014 ◽  
Vol 106 (5) ◽  
pp. 151-165 ◽  
Author(s):  
Petra Sehnalová ◽  
Soňa Legartová ◽  
Dušan Cmarko ◽  
Stanislav Kozubek ◽  
Eva Bártová

2018 ◽  
Vol 25 (23) ◽  
pp. 2722-2735 ◽  
Author(s):  
Barbara Bukowska ◽  
Boleslaw T. Karwowski

The clustered DNA lesions are a characteristic feature of ionizing radiation and are defined as two or more damage sites formed within 20 bps after the passage of a single radiation track. The clustered DNA lesions are divided into two major groups: double-stranded breaks (DSBs) and non-DSB clusters also known as Oxidatively-induced Clustered DNA Lesions (OCDLs), which could involve either two opposing strands or the same strand. As irradiation is gaining greater interest in cancer treatment as well as in imaging techniques, the detailed knowledge of its genotoxicity and the mechanisms of repair of radiation-induced DNA damage remain issues to explore. In this review we look at the ways the cell copes with clustered DNA lesions, especially with 5′,8-cyclo-2′-deoxypurines. As the base excision repair deals with isolated lesions, complex damage is more difficult to repair. Depending on the number of lesions within a cluster, their types and mutual distribution, long-patch BER or NER are activated. During the repair of opposing lesions, DSBs could be generated, which are repaired either by nonhomologous end joining (NHEJ) or homologous recombination (HR). The repair of individual lesions within a cluster progresses gradually. This slower processing of particular damage might lead to severe biological consequences such as misrepair, mutations and chromosomal rearrengement as it enhances the plausibility of a cluster encountering a replication fork prior to its repair. The consequences of clustered DNA lesions on cell survival and their relevance to the efficacy and safety of radiotherapy and radiodiagnosis will also be discussed.


2018 ◽  
Vol 53 (4) ◽  
pp. 241-248 ◽  
Author(s):  
J.-L. Ravanat

During the last few decades, a considerable amount of work has been done to better assess the effects of ionizing radiation on living organisms. In particular a lot of attention has been focused on the consequences of modifications of the DNA macromolecule, the support of the genetic information. Detailed information is now available on the formation of radiation-induced DNA lesions at the physical, chemical and biological levels. Emphasis will be placed in this review article on the differences and similarities, in term of DNA lesions formation and outcome, between endogenous oxidative stress and ionizing radiation, both stresses that could produce oxidative DNA lesions through similar mechanistic pathways involving mostly reactive oxygen species. If the chemical nature of the generated lesions is similar, the differences in term of biological consequences could be attributed to their spatial distribution in genomic DNA, since ionizing radiations produce lesions in cluster. These clusters of lesions represent a challenge for the DNA repair machinery. In contrast, endogenous oxidative stress generates scattered lesions that could be repaired with a much higher efficacy and fidelity. Possible implication of the use of DNA damage and repair for human health purposes and radiological protection will be discussed.


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