The Molecular and Genetic Effects of Ultraviolet Radiation Exposure on Skin Cells
Henry W. Lim, Herbert Hönigsmann, John L. M. Hawk in Photodermatology, 2007
DNA that has modified bases (such as 8oG) is repaired by base excision repair, which replaces only the damaged base and a few neighboring bases. In either case, the opposite undamaged strand of DNA is used as a template to resynthesize the DNA sequence. This type of DNA repair occurs at anytime nearly anywhere in the genome [global genomic repair (GGR)]. However, localized regions of transcribed DNA are repaired much faster by a group of proteins performing transcription-coupled repair (TCR). They are attracted to the site by a transcription fork that has stalled, and TCR accelerates repair of the transcribed strand. If a lesion is not repaired by the time the DNA must be replicated, damage-specific polymerases eta or zeta can insert bases to allow continued replication in a process called translesion synthesis (4). If all these measures fail and too much DNA damage remains, the cell activates a suicide pathway call apoptosis.
Introduction to Genomics
Altuna Akalin in Computational Genomics with R, 2020
Mutations in the genome occur due to multiple reasons. First, DNA replication is not an error-free process. Before a cell division, the DNA is replicated with 1 mistake per 10^8 to 10^10 base-pairs. Second, mutagens such as UV light can induce mutations on the genome. The third factor that contributes to mutation is imperfect DNA repair. Every day, any human cell suffers multiple instances of DNA damage. DNA repair enzymes are there to cope with this damage but they are also not error-free, depending on which DNA repair mechanism is used (there are multiple), mistakes will be made at varying rates.
Radiation Toxicity
Frank A. Barile in Barile’s Clinical Toxicology, 2019
UV rays are of lower frequency and longer wavelength than ionizing radiation (about 10−8 to 10−7 meters; Figure 33.1). Thus, the effects of UV radiation are less penetrating and benign. Unlike ionizing radiation, skin damage induced by UV rays (e.g., from sun exposure) is mediated principally by the generation of reactive oxygen species (ROS) and the interruption of melanin production. As with ionizing radiation, however, cumulative or intense exposure to UV rays precipitates DNA mutations—that is, base pair insertions, deletions, single-strand breaks, and DNA–protein cross-links. DNA repair mechanisms play an important role in correcting UV-induced DNA damage and preventing further consequences of excessive sunburn. Melanin production by melanocytes increases, and the epidermis thickens in an attempt to prevent future damaging effects. The protective ability of antioxidant enzymes and DNA repair pathways diminishes with age, thus setting the conditions for the development of skin neoplasms later in life.
Evaluating the influences of confounding variables on benchmark dose using a case study in the field of ionizing radiation
Published in International Journal of Radiation Biology, 2022
Nadine Adam, Ngoc Q. Vuong, Hailey Adams, Byron Kuo, Afshin Beheshti, Carole Yauk, Ruth Wilkins, Vinita Chauhan
The 412 genes modeled by BMD across all groups were associated with a total of 25 pathways. An accumulation plot of the total pathways and their associated BMD median values show that the M-NS curve had a unique profile in comparison to the other three groups, where more pathways fit models at lower BMD values (Figure 5B, green curve). There were 14 (F-NS) and 19 (M-NS) pathway BMDs derived for the nonsmoker groups, and 15 (F-S) and 11 (M-S) pathways for the smoker groups (Figure 6A and 7, and Table S2). A total of one (F-NS), seven (M-NS), one (F-S), and two (M-S) unique pathway(s) were identified for each of the groups. However, the majority of these unique pathways displayed broad confidence intervals (Figure S1). Three pathways with narrow confidence intervals included: “Damage Bypass,” “Translesion Synthesis of POLH” and “Translesion Synthesis by Y family DNA polymerases bypasses lesions on DNA template,” which were modeled only in the male nonsmoker group. Nine of the 25 pathways (36%) were common to all four groups (Figure 6A and 7 and Table S2), and an additional 20% were common to at least two groups. Hierarchical cluster analysis of the BMDs of the nine common pathways shows some small differences between males and females as well as smokers and nonsmokers (Figure 6B); however, pathway BMDL to BMDU plots for each pathway were largely overlapping (Figure S1).
Prospects of topical protection from ultraviolet radiation exposure: a critical review on the juxtaposition of the benefits and risks involved with the use of chemoprotective agents
Published in Journal of Dermatological Treatment, 2018
Nilutpal Sharma Bora, Bhaskar Mazumder, Pronobesh Chattopadhyay
Another avenue which is being explored by researchers is the inclusion of topical antioxidants and DNA repair stimulants which prove to be beneficial for improving the photoprotective properties of sunscreen formulations. Antioxidants that can be administered via the dermal route, like reservatrol, flavonoids, and green tea extracts may prove to be advantageous in reducing skin damage caused by UV rays, despite the fact that these are chemically unstable and poorly diffuse into the epidermal layer (100–103). T4 endonuclease and photolyase which are two important DNA repair enzymes have proven to decrease the UV-related DNA damage (104–106). Thymidine dinucleotides stimulate the DNA repair response mechanism if administered prior to UV exposure and helps in curbing the DNA damage caused by UV radiation (107).
Discovery of small-molecule ATR inhibitors for potential cancer treatment: a patent review from 2014 to present
Published in Expert Opinion on Therapeutic Patents, 2022
Suwen Hu, Zi Hui, Jilong Duan, Carmen Garrido, Tian Xie, Xiang-Yang Ye
Although both monotherapy and combination therapy are backed by the results in preclinical studies, the monotherapy is likely have limited anticancer efficacy. On the other hand, the combination therapy has demonstrated to be the focuses for the pharmaceutical industries with the current concept of synthetic lethality. Synergistic anticancer effects have been shown in different cancer types in both preclinical studies and clinical studies [11,12,74–76]. Because genomic instability is a hallmark of cancer, drugs that target defective DNA repair and deregulated transcription may be specifically toxic (synthetically lethal) for cancer cells. The discussed patented drugs could be used in combination with other therapies (i.e. associating DNA repair and DNA damage-based drugs) found in specific cancer types.