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International Journal of Environmental... Oct 2022Occupational exposure may involve a variety of toxic compounds. A mutagenicity analysis using the Ames test can provide valuable information regarding the toxicity of... (Review)
Review
Occupational exposure may involve a variety of toxic compounds. A mutagenicity analysis using the Ames test can provide valuable information regarding the toxicity of absorbed xenobiotics. Through a search of relevant databases, this systematic review gathers and critically discusses the published papers (excluding other types of publications) from 2001-2021 that have assessed urinary mutagenicity (Ames test with ) in an occupational exposure context. Due to the heterogeneity of the study methods, a meta-analysis could not be conducted. The characterized occupations were firefighters, traffic policemen, bus drivers, mail carriers, coke oven and charcoal workers, chemical laboratory staff, farmers, pharmacy workers, and professionals from several other industrial sectors. The genetically modified bacterial strains (histidine dependent) TA98, TA100, YG1041, YG1021, YG1024 and YG1042 have been used for the health risk assessment of individual (e.g., polycyclic aromatic hydrocarbons) and mixtures of compounds (e.g., diesel engine exhaust, fire smoke, industrial fumes/dyes) in different contexts. Although comparison of the data between studies is challenging, urinary mutagenicity can be very informative of possible associations between work-related exposure and the respective mutagenic potential. Careful interpretation of results and their direct use for occupational health risk assessment are crucial and yet complex; the use of several strains is highly recommended since individual and/or synergistic effects of complex exposure to xenobiotics can be overlooked. Future studies should improve the methods used to reach a standardized protocol for specific occupational environments to strengthen the applicability of the urinary mutagenicity assay and reduce inter- and intra-individual variability and exposure source confounders.
Topics: Humans; Mutagens; Mutagenicity Tests; Coke; Charcoal; Histidine; Vehicle Emissions; Polycyclic Aromatic Hydrocarbons; Smoke; Coloring Agents
PubMed: 36293654
DOI: 10.3390/ijerph192013074 -
PloS One 2016Sperm DNA fragmentation has been associated with reduced fertilization rates, embryo quality, pregnancy rates and increased miscarriage rates. Various methods exist to... (Meta-Analysis)
Meta-Analysis Review
Sperm DNA fragmentation has been associated with reduced fertilization rates, embryo quality, pregnancy rates and increased miscarriage rates. Various methods exist to test sperm DNA fragmentation such as the sperm chromatin structure assay (SCSA), the sperm chromatin dispersion (SCD) test, the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labelling (TUNEL) assay and the single cell gel electrophoresis (Comet) assay. We performed a systematic review and meta-analysis to assess the value of measuring sperm DNA fragmentation in predicting chance of ongoing pregnancy with IVF or ICSI. Out of 658 unique studies, 30 had extractable data and were thus included in the meta-analysis. Overall, the sperm DNA fragmentation tests had a reasonable to good sensitivity. A wide variety of other factors may also affect the IVF/ICSI outcome, reflected by limited to very low specificity. The constructed hierarchical summary receiver operating characteristic (HSROC) curve indicated a fair discriminatory capacity of the TUNEL assay (area under the curve (AUC) of 0.71; 95% CI 0.66 to 0.74) and Comet assay (AUC of 0.73; 95% CI 0.19 to 0.97). The SCSA and the SCD test had poor predictive capacity. Importantly, for the TUNEL assay, SCD test and Comet assay, meta-regression showed no differences in predictive value between IVF and ICSI. For the SCSA meta-regression indicated the predictive values for IVF and ICSI were different. The present review suggests that current sperm DNA fragmentation tests have limited capacity to predict the chance of pregnancy in the context of MAR. Furthermore, sperm DNA fragmentation tests have little or no difference in predictive value between IVF and ICSI. At this moment, there is insufficient evidence to recommend the routine use of sperm DNA fragmentation tests in couples undergoing MAR both for the prediction of pregnancy and for the choice of treatment. Given the significant limitations of the evidence and the methodological weakness and design of the included studies, we do urge for further research on the predictive value of sperm DNA fragmentation for the chance of pregnancy after MAR, also in comparison with other predictors of pregnancy after MAR.
Topics: Abortion, Spontaneous; Chromatin; Comet Assay; DNA Fragmentation; Female; Fertilization in Vitro; Humans; In Situ Nick-End Labeling; Male; Pregnancy; Pregnancy Rate; Semen Analysis; Spermatozoa
PubMed: 27832085
DOI: 10.1371/journal.pone.0165125 -
British Journal of Cancer Feb 2012The cytokinesis-block micronucleus test (MNT), as a marker of chromosomal mutagen sensitivity, was applied in a number of studies enrolling breast cancer (BC) patients... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The cytokinesis-block micronucleus test (MNT), as a marker of chromosomal mutagen sensitivity, was applied in a number of studies enrolling breast cancer (BC) patients and subjects with known or putative genetic predisposition to BC. The large majority of them involve the evaluation of induced micronuclei (MN) frequency in peripheral lymphocytes, after the in vitro challenge with ionising radiations.
METHODS
The aim of the present systematic review and meta-analysis is to investigate the role of MN assay in the identification of individuals at increased risk of BC and its potential use as prescreening test in women with a family history (FH) of BC.
RESULTS
Twelve studies were included in the meta-analysis, covering a time interval 1998-2007, and including 752 cases and 593 controls. Among the cases, 629 are cancer patients and 123 are cancer-free subjects, including 32 first-degree relatives of the susceptible subjects and 91 BRCA1/2 mutation carriers. Our meta-analysis reveals a significant increase of baseline MN frequency related to cancer status, but the association with FH of BC and specifically with BRCA mutations is not clear. A larger difference in MN frequency between cases and controls was observed after in vitro challenge, but response to radiation exposure doesn't appear to better discriminate cancer-susceptible subjects.
CONCLUSION
Our study suggests the presence of some bias affecting many of these studies, reinforcing the suggestion that a more rigorous study design is needed in this area.
Topics: Breast Neoplasms; Family Health; Female; Genes, BRCA1; Genes, BRCA2; Humans; Micronucleus Tests; Mutation
PubMed: 22187037
DOI: 10.1038/bjc.2011.567 -
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 -
Biomedical Papers of the Medical... Mar 2024Oxidative DNA damage markers (8OHdG, comet assay, gammaH2AX) are becoming widely used in clinical cardiology research. To conduct this review of DNA damage in relation... (Meta-Analysis)
Meta-Analysis Review
Oxidative DNA damage markers (8OHdG, comet assay, gammaH2AX) are becoming widely used in clinical cardiology research. To conduct this review of DNA damage in relation to hypertension in humans, we used databases (e.g. PubMed, Web of Science) to search for English-language publications up to June 30, 2022 and the terms: DNA damage, comet assay, gammaH2AX, 8OHdG, strand breaks, and arterial hypertension. Exclusion criteria were: children, absence of relevant controls, extra-arterial hypertensive issues, animal, cell lines. From a total of 79526, 15 human studies were selected. A total of 902 hypertensive patients (pts): (comet: N=418 pts; 8OHdG: N=484 pts) and 587 controls (comet: N=203; 8OHdG: N=384) were included. DNA damage was significantly higher in hypertensive pts than healthy controls (comet 26.6±11.0 vs 11.7±4.07 arbitrary units /A.U./; P<0.05 and="" 8ohdg="" 13="" 1="" 4="" 12="" vs="" 6="" 97="" 2="" 67="" ng="" mg="" creatinine="" i=""> P<0.05) confirmed with meta-analysis for both. Greater DNA damage was observed in more adverse cases (concentric cardiac hypertrophy 43.4±15.4 vs 15.6±5.5; sustained/untreated hypertension 31.4±12.1 vs 14.2±5/35.0±5.0 vs 25.0 ±5.0; non-dippers 39.2±15.5 vs 29.4±11.1 A.U.; elderly 14.9±4.5 vs 9.3±4.1 ng/mg creatinine; without carvedilol 9.1±4.2 vs 5.7±3.9; with coronary heart disease 0.5±0.1 vs 0.2±0.1 ng/mL) (P<0.05) confirmed with meta-analysis. DNA damage correlated strongly positively with serum glycosylated haemoglobin (r=0.670; P<0.05) and negatively with total antioxidant status (r=-0.670 to -0.933; P<0.05). This is the first systematic review with meta-analysis showing that oxidative DNA damage was increased in humans with arterial hypertension compared to controls.
Topics: Child; Animals; Humans; Aged; 8-Hydroxy-2'-Deoxyguanosine; Creatinine; DNA Damage; Comet Assay; Hypertension
PubMed: 37916467
DOI: 10.5507/bp.2023.044 -
Asian Journal of Andrology 2017Sperm DNA damage is prevalent among infertile men and is known to influence natural reproduction. However, the impact of sperm DNA damage on assisted reproduction... (Meta-Analysis)
Meta-Analysis Review
Sperm DNA damage is prevalent among infertile men and is known to influence natural reproduction. However, the impact of sperm DNA damage on assisted reproduction outcomes remains controversial. Here, we conducted a meta-analysis of studies on sperm DNA damage (assessed by SCSA, TUNEL, SCD, or Comet assay) and clinical pregnancy after IVF and/or ICSI treatment from MEDLINE, EMBASE, and PUBMED database searches for this analysis. We identified 41 articles (with a total of 56 studies) including 16 IVF studies, 24 ICSI studies, and 16 mixed (IVF + ICSI) studies. These studies measured DNA damage (by one of four assays: 23 SCSA, 18 TUNEL, 8 SCD, and 7 Comet) and included a total of 8068 treatment cycles (3734 IVF, 2282 ICSI, and 2052 mixed IVF + ICSI). The combined OR of 1.68 (95% CI: 1.49-1.89; P < 0.0001) indicates that sperm DNA damage affects clinical pregnancy following IVF and/or ICSI treatment. In addition, the combined OR estimates of IVF (16 estimates, OR = 1.65; 95% CI: 1.34-2.04; P < 0.0001), ICSI (24 estimates, OR = 1.31; 95% CI: 1.08-1.59; P = 0.0068), and mixed IVF + ICSI studies (16 estimates, OR = 2.37; 95% CI: 1.89-2.97; P < 0.0001) were also statistically significant. There is sufficient evidence in the existing literature suggesting that sperm DNA damage has a negative effect on clinical pregnancy following IVF and/or ICSI treatment.
Topics: Comet Assay; DNA Damage; DNA Fragmentation; Female; Fertilization in Vitro; Humans; In Situ Nick-End Labeling; Infertility, Male; Male; Pregnancy; Pregnancy Rate; Sperm Injections, Intracytoplasmic; Spermatozoa
PubMed: 27345006
DOI: 10.4103/1008-682X.182822 -
Mutation Research. Genetic Toxicology... Oct 2023Can human peripheral blood cells be used as a surrogate for bone marrow cells, in evaluating the genotoxic effects of stressors? We searched the Pubmed/Medline and... (Meta-Analysis)
Meta-Analysis Review
Can human peripheral blood cells be used as a surrogate for bone marrow cells, in evaluating the genotoxic effects of stressors? We searched the Pubmed/Medline and PubChem databases to identify publications relevant to this question. Micronucleus formation was the genotoxicity endpoint. Three publications comparing exposed vs. non-exposed individuals are included in this analysis; the exposures were to ethylene oxide or ionising radiation (atomic bomb, thorotrast, or radioiodine therapy). Information was extracted on the types of exposure, the numbers of participants, and the micronucleus frequencies. Relative differences (odds ratios) and absolute differences (risk differences) in the numbers of micronuclei between exposed and non-exposed persons were calculated separately for individual cell types (peripheral blood and bone marrow). Random effects meta-analyses for the relative differences in cell abnormalities were performed. The results showed very small differences in the frequencies of micronuclei between exposed and non-exposed individuals, as measured in either peripheral blood or bone marrow cell populations, on both absolute and relative scales. No definite conclusion concerning the relative sensitivities of bone marrow and peripheral blood cells can be made, based on these publications.
Topics: Humans; Bone Marrow; Iodine Radioisotopes; Micronucleus Tests; Blood Cells; Bone Marrow Cells; DNA Damage; Micronuclei, Chromosome-Defective
PubMed: 37770146
DOI: 10.1016/j.mrgentox.2023.503689 -
International Journal of Environmental... Jan 2020Antineoplastic drugs (ANDs) are a broad group of chemicals showing, at the same time, carcinogenic effects. The potential, albeit true, risk of side effects cannot be... (Review)
Review Meta-Analysis
BACKGROUND
Antineoplastic drugs (ANDs) are a broad group of chemicals showing, at the same time, carcinogenic effects. The potential, albeit true, risk of side effects cannot be accepted, especially if resulting from occupational exposure. The aim of this study was to evaluate the association between occupational exposure to ANDs and the extent of primary DNA damage in health professionals.
METHODS
A systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed/Medline, Web of Science, and Scopus were used to perform the literature search. The databases were examined in July 2019. Sub-group, moderator, and cumulative analyses were conducted. The trim and fill method was used in the case of potential publication bias.
RESULTS
Twenty studies were included in the qualitative analysis, and 19 in quantitative evaluation. The pooled effect size was 1.27 [(95% confidence interval (CI) = 0.66-1.88), = 0.000] based on 1569 subjects. The moderator analysis by duration of exposure showed a positive association between duration of exposure and primary DNA damage.
CONCLUSIONS
This systematic review clearly shows a significant association between occupational exposure to ANDs and the extent of primary DNA damage in health professionals. Considering these results, health professionals should be warned against this potential occupational risk.
Topics: Antineoplastic Agents; Comet Assay; DNA Damage; Health Personnel; Humans; Occupational Exposure
PubMed: 31947621
DOI: 10.3390/ijerph17020523 -
Mutation Research. Reviews in Mutation... 2020The percentage of people affected by overweight, obesity and/or diabetes drastically increased within the last decades. This development is still ongoing, which puts a... (Meta-Analysis)
Meta-Analysis
The percentage of people affected by overweight, obesity and/or diabetes drastically increased within the last decades. This development is still ongoing, which puts a large part of our society at increased risk for diseases, such as cancer, cardiovascular diseases and cognitive impairment. Especially the development of type 2 diabetes and overweight/obesity could theoretically be prevented. The loss of DNA and genome stability is associated with the above-mentioned metabolic diseases. Insulin resistance, high blood glucose levels or increased body fat are linked to a chronically elevated inflammatory state. This amplifies oxidative stress, might lead to oxidative DNA damage, impairs the cellular proliferation process and results in mutations; all of which increase the possibility for the development of dysfunctional cells, tissue and organs. An established method to measure chromosomal damage is the cytokinesis block micronucleus (CBMN) cytome assay. The aim of this systematic review and meta-analysis is to collect and analyse the current literature of diabetic, obese and overweight patients and their link to cellular mutations measured by the CBMN assay. A clear trend towards increased genome damage in these metabolic diseases was observed. Significantly increased frequencies of chromosomal aberrations were seen in type 2 diabetic subjects (micronuclei frequency: SMD: 1.18, 95% CI: 0.76, 1.60; I = 84%). In both, type 1 and type 2 diabetics, disease progression as well as medical quality and quantity were linked to further elevated genome instability. In type 1 diabetic and overweight/obese subjects the number of studies is small and for valid and reliable results more data are needed. Besides the traditionally used material for this method, PBMCs, we extended our analysis to buccal cells in order to qualitatively compare the two cell types. Finally, we discuss knowledge as well as technical/methodical gaps of the CBMN cytome assay and its usability for clinical practice in these metabolic diseases.
Topics: Cell Proliferation; Chromosome Aberrations; Cognitive Dysfunction; Cytokinesis; DNA Damage; Diabetes Mellitus, Type 2; Humans; Micronuclei, Chromosome-Defective; Micronucleus Tests; Obesity; Oxidative Stress
PubMed: 33339574
DOI: 10.1016/j.mrrev.2020.108343 -
Mutation Research. Reviews in Mutation... 2016Accumulating evidence suggests that epigenetic alterations play an important role in chemically-induced carcinogenesis. Although the epigenome and genome may be equally... (Review)
Review
Accumulating evidence suggests that epigenetic alterations play an important role in chemically-induced carcinogenesis. Although the epigenome and genome may be equally important in carcinogenicity, the genotoxicity of chemical agents and exposure-related transcriptomic responses have been more thoroughly studied and characterized. To better understand the evidence for epigenetic alterations of human carcinogens, and the potential association with genotoxic endpoints, we conducted a systematic review of published studies of genotoxic carcinogens that reported epigenetic endpoints. Specifically, we searched for publications reporting epigenetic effects for the 28 agents and occupations included in Monograph Volume 100F of the International Agency for the Research on Cancer (IARC) that were classified as "carcinogenic to humans" (Group 1) with strong evidence of genotoxic mechanisms of carcinogenesis. We identified a total of 158 studies that evaluated epigenetic alterations for 12 of these 28 carcinogenic agents and occupations (1,3-butadiene, 4-aminobiphenyl, aflatoxins, benzene, benzidine, benzo[a]pyrene, coke production, formaldehyde, occupational exposure as a painter, sulfur mustard, and vinyl chloride). Aberrant DNA methylation was most commonly studied, followed by altered expression of non-coding RNAs and histone changes (totaling 85, 59 and 25 studies, respectively). For 3 carcinogens (aflatoxins, benzene and benzo[a]pyrene), 10 or more studies reported epigenetic effects. However, epigenetic studies were sparse for the remaining 9 carcinogens; for 4 agents, only 1 or 2 published reports were identified. While further research is needed to better identify carcinogenesis-associated epigenetic perturbations for many potential carcinogens, published reports on specific epigenetic endpoints can be systematically identified and increasingly incorporated in cancer hazard assessments.
Topics: Animals; Carcinogenicity Tests; Carcinogens; Environmental Exposure; Epigenesis, Genetic; Gene Expression Regulation; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Variation; Humans; Mutagenicity Tests; Mutagens; Occupational Exposure
PubMed: 27234561
DOI: 10.1016/j.mrrev.2016.03.004