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Sports Medicine (Auckland, N.Z.) Jan 2020Exercise is widely recognised for its health enhancing benefits. Despite this, an overproduction of reactive oxygen and nitrogen species (RONS), outstripping antioxidant... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Exercise is widely recognised for its health enhancing benefits. Despite this, an overproduction of reactive oxygen and nitrogen species (RONS), outstripping antioxidant defence mechanisms, can lead to a state of (chronic) oxidative stress. DNA is a vulnerable target of RONS attack and, if left unrepaired, DNA damage may cause genetic instability.
OBJECTIVE
This meta-analysis aimed to systematically investigate and assess the overall effect of studies reporting DNA damage following acute aerobic exercise.
METHODS
Web of Science, PubMed, MEDLINE, EMBASE, and Scopus were searched until April 2019. Outcomes included (1) multiple time-points (TPs) of measuring DNA damage post-exercise, (2) two different quantification methods (comet assay and 8-oxo-2'-deoxyguanosine; 8-OHdG), and (3) protocols of high intensity (≥ 75% of maximum rate of oxygen consumption; VO) and long distance (≥ 42 km).
RESULTS
Literature search identified 4316 non-duplicate records of which 35 studies were included in the meta-analysis. The evidence was strong, showcasing an increase in DNA damage immediately following acute aerobic exercise with a large-effect size at TP 0 (0 h) (SMD = 0.875; 95% CI 0.5, 1.25; p < 0.05). When comparing between comet assay and 8-OHdG at TP 0, a significant difference was observed only when using the comet assay. Finally, when isolating protocols of long-distance and high-intensity exercise, increased DNA damage was only observed in the latter. (SMD = 0.48; 95% CI - 0.16, 1.03; p = 0.15 and SMD = 1.18; 95% CI 0.71, 1.65; p < 0.05 respectively).
CONCLUSIONS
A substantial increase in DNA damage occurs immediately following acute aerobic exercise. This increase remains significant between 2 h and 1 day, but not within 5-28 days post-exercise. Such an increase was not observed in protocols of a long-distance. The relationship between exercise and DNA damage may be explained through the hormesis theory, which is somewhat one-dimensional, and thus limited. The hormesis theory describes how exercise modulates any advantageous or harmful effects mediated through RONS, by increasing DNA oxidation between the two end-points of the curve: physical inactivity and overtraining. We propose a more intricate approach to explain this relationship: a multi-dimensional model, to develop a better understanding of the complexity of the relationship between DNA integrity and exercise.
Topics: DNA Damage; Exercise; Humans
PubMed: 31529301
DOI: 10.1007/s40279-019-01181-y -
Iranian Journal of Public Health Aug 2023Asbestos is one of the most important environmental and occupational carcinogens. Nevertheless, the mechanisms by which asbestos fiber exposure causes chronic diseases... (Review)
Review
BACKGROUND
Asbestos is one of the most important environmental and occupational carcinogens. Nevertheless, the mechanisms by which asbestos fiber exposure causes chronic diseases are not fully understood. We performed the first systematic review on the epidemiological evidence to examine the association between occupational exposure to asbestos and oxidative stress and DNA damage.
METHODS
In this systematic review study, the PubMed and Scopus databases were searched for English-language publications. Eleven cross-sectional studies were included in the systematic review. A literature search was conducted by the main keywords including "Asbestos", "crocidolite", "chrysotile", "amphibole", "amosite", "Oxidative Stress", "DNA Damage", and "DNA injury". To evaluate the quality of studies, the "Newcastle-Ottawa Quality Assessment Scale" (NOS) was used.
RESULTS
Overall, 1235 articles were achieved by searching in databases. Finally, by considering the inclusion, and exclusion criteria, 11 articles were conducted for this study. These studies were published between 1986 and 2020. Oxidative stress and DNA damage can occur in exposure to asbestos. Among various biomarkers, 8-OHdG is the best. The analysis of 8-oxodG in asbestos workers can help identify subjects with a higher level of genotoxic damage.
CONCLUSION
This systematic review suggests that oxidative stress and DNA damage are two main outputs of asbestos exposure. Therefore, oxidative stress and DNA damage biomarkers can be used for identifying subjects at higher risk of cancer. These findings support policy initiatives aimed at detecting and eliminating asbestos fiber exposure and preventing potential health hazards in occupational settings.
PubMed: 37744536
DOI: 10.18502/ijph.v52i8.13400 -
Mutation Research. Reviews in Mutation... 2020Auto-immune diseases (AUD) are characterized by an immune response to antigenic components of the host itself. The etiology of AUD is not well understood. The available... (Meta-Analysis)
Meta-Analysis
Auto-immune diseases (AUD) are characterized by an immune response to antigenic components of the host itself. The etiology of AUD is not well understood. The available evidence points to an interaction between genetic, epigenetic, environmental, infectious and life-style factors. AUD are more prevalent in women than in men; sex hormones play a crucial role in this sex bias. Micronuclei (MN) emerged as a new player in the induction of AUD, based on the capacity of DNA-sensors to detect self-DNA that leaks into the cytoplasm from disrupted MN and induce the cGAS-STING pathway triggering an innate auto-immune response and chronic inflammation. It was found that inflammation can induce MN and MN can induce inflammation, leading to a vicious inflammation-oxidative-DNA damage-MN-formation-chromothripsis cycle. MN originating from sex chromosome-loss may induce inflammation and AUD. We performed a systematic review of studies reporting MN in patients with systemic or organ-specific AUD. A meta-analysis was performed on lymphocyte MN in diabetes mellitus (10 studies, 457 patients/290 controls) and Behcet's disease (3 studies, 100 patients/70 controls) and for buccal MN in diabetes mellitus (11 studies, 507 patients/427 controls). A statistically significant increase in patients compared to controls was found in the meta-analyses providing an indication of an association between MN and AUD. A 36%-higher mean-MRi in buccal cells (3.8+/-0.7) was found compared to lymphocytes (2.8+/-0.7)(P = 0.01). The meta-MRi in lymphocytes and buccal cells (1.7 and 3.0 respectively) suggest that buccal cells may be more sensitive. To assess their relative sensitivity, studies with measurements from the same subjects would be desirable. It is important that future studies (i) investigate, in well-designed powered studies, the prospective association of MN-formation with AUD and (ii) explore the molecular mechanisms by which chromosome shattering in MN and the release of chromatin fragments from MN lead to the formation of auto-antibodies.
Topics: Autoimmune Diseases; Chromothripsis; Female; Humans; Inflammation; Lymphocytes; Male; Micronuclei, Chromosome-Defective; Micronucleus Tests
PubMed: 33339583
DOI: 10.1016/j.mrrev.2020.108335 -
Open Medicine (Warsaw, Poland) 2023Today, in the modern world, people are often exposed to electromagnetic waves, which can have undesirable effects on cell components that lead to differentiation and... (Review)
Review
Today, in the modern world, people are often exposed to electromagnetic waves, which can have undesirable effects on cell components that lead to differentiation and abnormalities in cell proliferation, deoxyribonucleic acid (DNA) damage, chromosomal abnormalities, cancers, and birth defects. This study aimed to investigate the effect of electromagnetic waves on fetal and childhood abnormalities. PubMed, Scopus, Web of Science, ProQuest, Cochrane Library, and Google Scholar were searched on 1 January 2023. The Cochran's -test and statistics were applied to assess heterogeneity, a random-effects model was used to estimate the pooled odds ratio (OR), standardized mean difference (SMD), and mean difference for different outcomes, and a meta-regression method was utilized to investigate the factors affecting heterogeneity between studies. A total of 14 studies were included in the analysis, and the outcomes investigated were: change in gene expression, oxidant parameters, antioxidant parameters, and DNA damage parameters in the umbilical cord blood of the fetus and fetal developmental disorders, cancers, and childhood development disorders. Totally, the events of fetal and childhood abnormalities were more common in parents who have been exposed to EMFs compared to those who have not (SMD and 95% confidence interval [CI], 0.25 [0.15-0.35]; , 91%). Moreover, fetal developmental disorders (OR, 1.34; CI, 1.17-1.52; , 0%); cancer (OR, 1.14; CI, 1.05-1.23; , 60.1%); childhood development disorders (OR, 2.10; CI, 1.00-3.21; , 0%); changes in gene expression (mean difference [MD], 1.02; CI, 0.67-1.37; , 93%); oxidant parameters (MD, 0.94; CI, 0.70-1.18; , 61.3%); and DNA damage parameters (MD, 1.01; CI, 0.17-1.86; , 91.6%) in parents who have been exposed to EMFs were more than those in parents who have not. According to meta-regression, publication year has a significant effect on heterogeneity (coefficient: 0.033; 0.009-0.057). Maternal exposure to electromagnetic fields, especially in the first trimester of pregnancy, due to the high level of stem cells and their high sensitivity to this radiation, the biochemical parameters of the umbilical cord blood examined was shown increased oxidative stress reactions, changes in protein gene expression, DNA damage, and increased embryonic abnormalities. In addition, parental exposure to ionizing and non-ionizing radiation can lead to the enhancement of different cell-based cancers and developmental disorders such as speech problems in childhood.
PubMed: 37197358
DOI: 10.1515/med-2023-0697 -
Mutation Research. Reviews in Mutation... 2022Carbon black exposure causes oxidative stress, inflammation and genotoxicity. The objective of this systematic review was to assess the contributions of primary (i.e.... (Meta-Analysis)
Meta-Analysis Review
Carbon black exposure causes oxidative stress, inflammation and genotoxicity. The objective of this systematic review was to assess the contributions of primary (i.e. direct formation of DNA damage) and secondary genotoxicity (i.e., DNA lesions produced indirectly by inflammation) to the overall level of DNA damage by carbon black. The database is dominated by studies that have measured DNA damage by the comet assay. Cell culture studies indicate a genotoxic action of carbon black, which might be mediated by oxidative stress. Many in vivo studies originate from one laboratory that has investigated the genotoxic effects of Printex 90 in mice by intra-tracheal instillation. Meta-analysis and pooled analysis of these results demonstrate that Printex 90 exposure is associated with a slightly increased level of DNA strand breaks in bronchoalveolar lavage cells and lung tissue. Other types of genotoxic damage have not been investigated as thoroughly as DNA strand breaks, although there is evidence to suggest that carbon black exposure might increase the mutation frequency and cytogenetic endpoints. Stratification of studies according to concurrent inflammation and DNA damage does not indicate that carbon black exposure gives rise to secondary genotoxicity. Even substantial pulmonary inflammation is at best only associated with a weak genotoxic response in lung tissue. In conclusion, the review indicates that nanosized carbon black is a weak genotoxic agent and this effect is more likely to originate from a primary genotoxic mechanism of action, mediated by e.g., oxidative stress, than inflammation-driven (secondary) genotoxicity.
Topics: Mice; Animals; Soot; Comet Assay; DNA Damage; Nanoparticles; Inflammation; Mammals
PubMed: 36007825
DOI: 10.1016/j.mrrev.2022.108441 -
Biology Apr 2023Senescence is a cellular aging process in all multicellular organisms. It is characterized by a decline in cellular functions and proliferation, resulting in increased... (Review)
Review
BACKGROUND
Senescence is a cellular aging process in all multicellular organisms. It is characterized by a decline in cellular functions and proliferation, resulting in increased cellular damage and death. These conditions play an essential role in aging and significantly contribute to the development of age-related complications. Humanin is a mitochondrial-derived peptide (MDP), encoded by mitochondrial DNA, playing a cytoprotective role to preserve mitochondrial function and cell viability under stressful and senescence conditions. For these reasons, humanin can be exploited in strategies aiming to counteract several processes involved in aging, including cardiovascular disease, neurodegeneration, and cancer. Relevance of these conditions to aging and disease: Senescence appears to be involved in the decay in organ and tissue function, it has also been related to the development of age-related diseases, such as cardiovascular conditions, cancer, and diabetes. In particular, senescent cells produce inflammatory cytokines and other pro-inflammatory molecules that can participate to the development of such diseases. Humanin, on the other hand, seems to contrast the development of such conditions, and it is also known to play a role in these diseases by promoting the death of damaged or malfunctioning cells and contributing to the inflammation often associated with them. Both senescence and humanin-related mechanisms are complex processes that have not been fully clarified yet. Further research is needed to thoroughly understand the role of such processes in aging and disease and identify potential interventions to target them in order to prevent or treat age-related conditions.
OBJECTIVES
This systematic review aims to assess the potential mechanisms underlying the link connecting senescence, humanin, aging, and disease.
PubMed: 37106758
DOI: 10.3390/biology12040558 -
BioMed Research International 2022Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder of UV radiation-induced damage repair that is characterized by photosensitivity and a propensity for... (Review)
Review
BACKGROUND
Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder of UV radiation-induced damage repair that is characterized by photosensitivity and a propensity for developing, among many others, skin cancers at an early age. This systematic review focused on the correlation between the clinical, pathological, and genetic aspects of XP and skin cancer.
METHODS
A systematic review was conducted through a literature search of online databases PubMed, Cochrane Library, SciELO, and Google Scholar. Search terms were "Xeroderma pigmentosum", "XP", "XPC", "Nucleotide excision repair", "NER", "POLH", "Dry pigmented skin", and "UV sensitive syndrome" meshed with the terms "Skin cancer", "Melanoma", and "NMSC".
RESULTS
After 504 abstracts screening, 13 full-text articles were assessed for eligibility, and 3 of them were excluded. Ten articles were selected for qualitative assessment.
CONCLUSIONS
Patients with XP usually suffer shorter lives due to skin cancer and neurodegenerative disease. Deletion/alteration of a distinct gene allele can produce different types of cancer. The XPC and XP-E variants are more likely to have skin cancer than patients in other complement groups, and the most common cause of death for these patients is skin cancer (metastatic melanoma or invasive SCC). Still, aggressive preventative measures to minimize UV radiation exposure can retard the course of the disease and improve the quality of life.
Topics: DNA Repair; Humans; Ichthyosis; Melanoma; Neurodegenerative Diseases; Quality of Life; Skin Neoplasms; Ultraviolet Rays; Xeroderma Pigmentosum
PubMed: 35898688
DOI: 10.1155/2022/8549532 -
Frontiers in Physiology 20238-Hydroxy-2'-deoxyguanosine (8-OHdG) is a byproduct of DNA oxidation resulting from free radical attacks. Paradoxically, treatment with 8-OHdG accelerates tissue...
8-Hydroxy-2'-deoxyguanosine (8-OHdG) is a byproduct of DNA oxidation resulting from free radical attacks. Paradoxically, treatment with 8-OHdG accelerates tissue healing. The aim of this study is to quantify the 8-OHdG response after a single session of exercise in both trained and untrained adults. A systematic review and meta-analysis of exercise intervention studies measuring changes in blood 8-OHdG following resistance exercise and aerobic exercise were conducted. The literature search included Web of Science, PubMed, BASE, and Scopus, with publications up to February 2023 included. Subgroup analysis of training status was also conducted. Sixteen studies involving 431 participants met the eligibility criteria. Resistance exercise showed a medium effect on increasing circulating 8-OHdG levels (SMD = 0.66, < 0.001), which was similar for both trained and untrained participants. However, studies on aerobic exercise presented mixed results. For trained participants, a small effect of aerobic exercise on increasing circulating 8-OHdG levels was observed (SMD = 0.42; < 0.001). In contrast, for untrained participants, a large effect of decreasing circulating 8-OHdG levels was observed, mostly after long-duration aerobic exercise (SMD = -1.16; < 0.05). Similar to resistance exercise, high-intensity aerobic exercise (5-45 min, ≥75% VO) significantly increased circulating 8-OHdG levels, primarily in trained participants. Pooled results from the studies confirm an increase in circulating 8-OHdG levels after resistance exercise. However, further studies are needed to fully confirm the circulating 8-OHdG response to aerobic exercise. Increases in 8-OHdG after high-intensity aerobic exercise are observed only in trained individuals, implicating its role in training adaptation. : [https://Systematicreview.gov/], identifier [CRD42022324180].
PubMed: 38028771
DOI: 10.3389/fphys.2023.1275867 -
Environmental Research Nov 2022The present systematic review aimed to evaluate the associations between welding fumes exposure and changes in oxidative stress [superoxide dismutase (SOD) and... (Meta-Analysis)
Meta-Analysis Review
The present systematic review aimed to evaluate the associations between welding fumes exposure and changes in oxidative stress [superoxide dismutase (SOD) and malondialdehyde (MDA)] and DNA damage [8-hydroxy-2'-deoxyguanosine (8-OHdG) and DNA-protein crosslink (DPC)] markers in professional welders (PROSPERO CRD42022298115). Six electronic bibliographic databases were searched from inception through September 2021 to identify observational epidemiological studies evaluating the association between welding fumes exposures and changes in oxidative stress and DNA damage in professional welders. Two reviewers independently assessed the risk of bias and certainty of the evidence. A narrative synthesis of results was conducted using the Synthesis Without Meta-analysis (SWiM) method. Pooled mean differences with 95% confidence intervals were calculated in a random-effects meta-analysis for the outcomes of interest in the review. From 450 studies identified through the search strategy, 14 observational epidemiological studies were included in the review. Most studies reported significantly higher welding fumes levels in welders than in controls. The narrative synthesis results of SOD showed a significant difference between welders and controls, while the meta-analysis results of MDA did not show a significant difference between the studied groups (MD = 0.26; 95% CI, -0.03, 0.55). The meta-analysis results of 8-OHdG (MD = 9.38; 95% CI, 0.55-18.21) and DPC (MD = 1.07; 95% CI, 0.14-2) revealed significantly differences between the studied groups. The included studies were at high risk of exclusion and confounding bias. The certainty of the evidence for oxidative stress and DNA damage results were very low and moderate, respectively. Exposure to welding fumes and metal particles is associated with DNA damage in professional welders, and 8-OHdG and DPC might be considered reliable markers to assess DNA damage resulting from exposure to welding fumes. We recommend, however, that the evaluation of oxidative stress resulting from welding fumes exposure not be solely based on MDA and SOD.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Air Pollutants, Occupational; Biomarkers; DNA Damage; Gases; Humans; Metal Workers; Occupational Exposure; Oxidative Stress; Superoxide Dismutase; Welding
PubMed: 36041537
DOI: 10.1016/j.envres.2022.114152 -
Chemico-biological Interactions Sep 2023As part of a systematic review of the non-cancer and cancer hazards of propylene dichloride (PDC), with a focus on potential carcinogenicity in workers following... (Review)
Review
As part of a systematic review of the non-cancer and cancer hazards of propylene dichloride (PDC), with a focus on potential carcinogenicity in workers following inhalation exposures, we determined that a mode of action (MOA)-centric framing of cancer effects was warranted. In our MOA analysis, we systematically reviewed the available mechanistic evidence for PDC-induced carcinogenesis, and we mapped biologically plausible MOA pathways and key events (KEs), as guided by the International Programme on Chemical Safety (IPCS)-MOA framework. For the identified pathways and KEs, biological concordance, essentiality of KEs, concordance of empirical observations among KEs, consistency, and analogy were evaluated. The results of this analysis indicate that multiple biologically plausible pathways may contribute to the cancer MOA for PDC, but that the relevant pathways vary by exposure route and level, tissue type, and species; further, more than one pathway may occur concurrently at high exposure levels. While several important data gaps exist, evidence from in vitro mechanistic studies, in vivo experimental animal studies, and ex vivo human tumor tissue analyses indicates that the predominant MOA pathway likely involves saturation of cytochrome p450 2E1 (CYP2E1)-glutathione (GSH) detoxification (molecular initiating event; MIE), accumulation of CYP2E1-oxidative metabolites, cytotoxicity, chronic tissue damage and inflammation, and ultimately tumor formation. Tumors may occur through several subsets of inflammatory KEs, including inflammation-induced aberrant expression of activation-induced cytidine deaminase (AID), which causes DNA strand breaks and mutations and can lead to tumors with a characteristic mutational signature found in occupational cholangiocarcinoma. Dose concordance analysis showed that low-dose mutagenicity (from any pathway) is not a driving MOA, and that prevention of target tissue damage and inflammation (associated with saturation of CYP2E1-GSH detoxification) is expected to also prevent the cascade of processes responsible for tumor formation.
Topics: Propane; Humans; DNA Damage; Carcinogens; Inflammation; Cytochrome P-450 CYP2E1; Metabolic Networks and Pathways; Carcinogenesis; Animals; Cholangiocarcinoma; Glutathione
PubMed: 36754223
DOI: 10.1016/j.cbi.2023.110382