-
Toxicology Mechanisms and Methods Jan 2022Silica nanoparticles (SiNPs) have been widely used in nanotechnology, and more attention has been paid to their safety evaluation. However, there are still inconsistent... (Meta-Analysis)
Meta-Analysis
Silica nanoparticles (SiNPs) have been widely used in nanotechnology, and more attention has been paid to their safety evaluation. However, there are still inconsistent conclusions about the genotoxicity of SiNPs. A systematic review was conducted to explore whether SiNPs have genotoxicity followed by a meta-analysis of and murine genotoxicity tests. A total of 26 eligible studies were identified in this meta-analysis through a detailed process of inclusion and exclusion, which included 9 studies, 15 studies, and 2 in both. The results of studies showed that SiNPs exposure significantly increased the indicators of the comet assay, such as tail DNA content (T DNA%), tail length (TL), and olive tail moment (OTM). Indicators of mutagenicity had not been affected studies, such as mutation frequency (MF) and micronucleus (MN) frequency. There was a significant increase in MN frequency, but there was no influence on T DNA% . Results of subgroup analysis indicated that size and treatment time of SiNPs were the associated factors genotoxicity. The size of SiNPs, <21 nm, induced more DNA damage than larger sized SiNPs. It could induce MN formation when the treatment time of SiNPs was <12 h, and even more DNA damage when the exposure time over 12 h. SiNPs can induce genotoxicity both and . Comet assay may be more sensitive to detect genotoxicity, and MN frequency may be more suitable to detect genotoxicity.
Topics: Animals; Comet Assay; DNA Damage; Mice; Nanoparticles; Nanotechnology; Silicon Dioxide
PubMed: 34350812
DOI: 10.1080/15376516.2021.1965277 -
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 -
Mutation Research. Reviews in Mutation... 2016Styrene is a building-block of several compounds used in a wide array of materials and products. The most important human exposure to this substance occurs in industrial... (Meta-Analysis)
Meta-Analysis Review
Styrene is a building-block of several compounds used in a wide array of materials and products. The most important human exposure to this substance occurs in industrial settings, especially among reinforced-plastics industry workers. The effect of occupational exposure to styrene on cytogenetics biomarkers has been previously reviewed with positive association observed for chromosomal aberrations, and inconclusive data for the micronucleus assay. Some limitations were noted in those studies, including inadequate exposure assessment and poor epidemiological design. Furthermore, in earlier studies micronuclei frequency was measured with protocols not as reliable as cytokinesis-block micronucleus (CBMN) assay. Aim of the present systematic review and meta-analysis is to investigate genomic instability and DNA damage as measured by the CBMN assay in lymphocytes of subjects exposed to styrene. A total of 11 studies published between 2004 and 2012 were included in the meta-analysis encompassing 479 styrene-exposed workers and 510 controls. The quality of each study was estimated by a quality scoring system which ranked studies according to the consideration of major confounders, exposure characterization, and technical parameters. An overall increase of micronuclei frequencies was found in styrene-exposure workers when compared to referents (meta-MR 1.34; 95% CI 1.18-1.52), with significant increases achieved in six individual studies. The consistency of results in individual studies, the independence of this result from major confounding factors and from the quality of the study strengthens the reliability of risk estimates and supports the use of the CBMN assay in monitoring genetic risk in styrene workers.
Topics: Case-Control Studies; Cytokinesis; Humans; Micronucleus Tests; Occupational Exposure; Styrene
PubMed: 27894694
DOI: 10.1016/j.mrrev.2016.06.003 -
Clinical Oral Investigations Jan 2018A systematic review of clinical studies to evaluate the frequency of micronuclei in the oral mucosa of smokers and non-smokers in adult patients was performed. (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVES
A systematic review of clinical studies to evaluate the frequency of micronuclei in the oral mucosa of smokers and non-smokers in adult patients was performed.
MATERIALS AND METHODS
A comprehensive search was carried out on MEDLINE via PubMeb, Scopus, Web of Science, LILACS, BBO, and Cochrane Library and SIGLE without restrictions. Dissertations and thesis were searched using the ProQuest Dissertations and Periodicos Capes Thesis Databases. We included only cross-sectional clinical trials that compared the frequency of micronuclei in the oral mucosa of smokers and non-smokers in adult patients.
DATA
After the removal of duplicates, 1338 articles were identified. After title and abstract screening, 35 studies remained. Eighteen studies were further excluded, whereas 17 studies remained for qualitative analysis and 16 for the meta-analysis of the primary and secondary outcomes. A significant difference in the frequency of micronuclei in smokers when compared to non-smokers was observed in the present study.
CONCLUSIONS
Despite the high variation in the methodology of the assessed studies, this study showed a higher frequency of micronuclei in exfoliated cells of smokers compared to non-smokers.
CLINICAL SIGNIFICANCE
The use of tobacco is associated with cytotoxic and genotoxic effects because a higher frequency of micronuclei in exfoliated cells of smokers was observed.
Topics: Humans; Micronucleus Tests; Mouth Mucosa; Smoking
PubMed: 29063385
DOI: 10.1007/s00784-017-2246-4 -
Medicina Oral, Patologia Oral Y Cirugia... Mar 2019The aim of this systematic review was to evaluate the frequency of micronuclei or other DNA damage in the oral mucosa of adults that have smokeless tobacco habits... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The aim of this systematic review was to evaluate the frequency of micronuclei or other DNA damage in the oral mucosa of adults that have smokeless tobacco habits compared to adults that not have these habits.
MATERIAL AND METHODS
We searched PubMed, Scopus, Web of Science, LILACS, BBO and Cochrane Library and SIGLE. We also surveyed gray literature. We included only clinical trials that compare the frequency of micronuclei or other DNA damage in the oral mucosa of adults that have smokeless tobacco habits compared to adults that not have these habits. Quality assessments of the selected trials were evaluated by two independent reviewers, using the Effective Public Health Practice Project - (EPHPP) with modifications.
RESULTS
After the database screening and removal of duplicates, 2574 studies were identified. After title screening, 172 studies remained, and this number was reduced to 25 after careful examination of the abstracts. The standardized mean difference of the frequency of micronuclei between groups was 1.88, with a 95% confidence interval of 1.40 to 2.36 (p < 0.00001). In all analyses heterogeneity was detected.
CONCLUSIONS
Despite the heterogeneity of studies, the frequency of micronuclei was significant bigger in adults who have the smokeless tobacco habit when compared to those not have this habit. The same occurred with the frequency of binucleated cells, karyolisis and karyorrhexis.
Topics: Adult; DNA Damage; Databases, Factual; Humans; Micronucleus Tests; Mouth Mucosa; Public Health; Smoking; Nicotiana; Tobacco, Smokeless
PubMed: 30818306
DOI: 10.4317/medoral.22846 -
Environmental Science and Pollution... Feb 2019Chlorine is considered the most used chemical agent for water disinfection worldwide. However, water chlorination can lead to by-product generation which can be toxic to...
Chlorine is considered the most used chemical agent for water disinfection worldwide. However, water chlorination can lead to by-product generation which can be toxic to humans. The present study aimed to perform a systematic review on the toxicity of trihalomethanes (THMs) through bioindicators of cytotoxicity, genotoxicity, and mutagenicity. The results showed that studies on the effects of THMs on DNA are a current research concern for evaluating the toxicity of the pure compounds and real samples involving several types including water for recreational use, reused water, and drinking water. THMs deleterious effects have been assessed using several biosystems, where the Ames test along with experimental animal models were the most cited. A wide range of THM concentrations have been tested. Nevertheless, DNA damage was demonstrated, highlighting the potential human health risk. Among the studied THMs, chloroform presented a different action mechanism when compared with brominated THMs, with the former being cytotoxic while brominated THMs (bromodichloromethane, bromoform, and dibromochloromethane) were cytotoxic, genotoxic, and mutagenic. The described evidence in this research highlights the relevance of this topic as a human health issue. Nevertheless, research aimed to represent THMs current exposure conditions in a more accurate way would be needed to understand the real impact on human health.
Topics: Animals; Chloroform; DNA Damage; Disinfection; Halogenation; Humans; Mutagenicity Tests; Trihalomethanes; Water Pollutants, Chemical
PubMed: 30607849
DOI: 10.1007/s11356-018-3949-z -
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 -
Human Reproduction (Oxford, England) Oct 2012Is there an association between high levels of sperm DNA damage and miscarriage? (Meta-Analysis)
Meta-Analysis Review
STUDY QUESTION
Is there an association between high levels of sperm DNA damage and miscarriage?
SUMMARY ANSWER
Miscarriage rates are positively correlated with sperm DNA damage levels.
WHAT IS KNOWN ALREADY
Most ejaculates contain a subpopulation of sperm with DNA damage, also referred to as DNA fragmentation, in the form of double or single-strand breaks which have been induced in the DNA prior to or following ejaculation. This DNA damage may be particularly elevated in some subfertile men, hence several studies have examined the link between sperm DNA damage levels and conception and miscarriage rates.
STUDY DESIGN, SIZE, DURATION
A systematic review and meta-analysis of studies which examined the effect of sperm DNA damage on miscarriage rates was performed. Searches were conducted on MEDLINE, EMBASE and the Cochrane Library without any language restrictions from database inception to January 2012.
PARTICIPANTS/MATERIALS, SETTING, METHODS
We used the terms 'DNA damage' or 'DNA fragmentation' combined with 'miscarriage', 'abortion' or 'pregnancy' to generate a set of relevant citations. Data extraction was performed by two reviewers. Study quality was assessed using the Newcastle-Ottawa Scale. Meta-analysis of relative risks of miscarriage was performed with a random effects model. Subgroup analyses were performed by the type of DNA damage test, whether the sperm examined were prepared or from raw semen and for pregnancies resulting from IVF or ICSI treatment.
MAIN RESULTS AND THE ROLE OF CHANCE
We identified 16 cohort studies (2969 couples), 14 of which were prospective. Eight studies used acridine orange-based assays, six the TUNEL assay and two the COMET assay. Meta-analysis showed a significant increase in miscarriage in patients with high DNA damage compared with those with low DNA damage [risk ratio (RR) = 2.16 (1.54, 3.03), P < 0.00001)]. A subgroup analysis showed that the miscarriage association is strongest for the TUNEL assay (RR = 3.94 (2.45, 6.32), P < 0.00001).
LIMITATIONS, REASONS FOR CAUTION
There is some variation in study characteristics, including the use of different assays and different thresholds for DNA damage and the definition of pregnancy loss.
WIDER IMPLICATIONS OF THE FINDINGS
The use of methods which select sperm without DNA damage for use in assisted conception treatment may reduce the risk of miscarriage. This finding indicates that assays detecting DNA damage could be considered in those suffering from recurrent pregnancy loss. Further research is necessary to study the mechanisms of DNA damage and the potential therapeutic effects of antioxidant therapy.
STUDY FUNDING/COMPETING INTEREST(S)
None.
Topics: Abortion, Spontaneous; Cohort Studies; Comet Assay; DNA Fragmentation; Female; Fertilization in Vitro; Humans; In Situ Nick-End Labeling; Male; Odds Ratio; Pregnancy; Risk Assessment; Sperm Injections, Intracytoplasmic; Spermatozoa; United States
PubMed: 22791753
DOI: 10.1093/humrep/des261 -
Mutation Research. Reviews in Mutation... 2016Many studies have reported the occurrence of work-environment contamination by antineoplastic drugs (ANPD), with significant incorporation of trace amounts of these... (Meta-Analysis)
Meta-Analysis Review
Occupational exposure to cytostatic/antineoplastic drugs and cytogenetic damage measured using the lymphocyte cytokinesis-block micronucleus assay: A systematic review of the literature and meta-analysis.
Many studies have reported the occurrence of work-environment contamination by antineoplastic drugs (ANPD), with significant incorporation of trace amounts of these hazardous drugs in hospital personnel. Given the ability of most ANPD to actively bind DNA, thus inducing genotoxic effects, it is of pivotal importance to assess the degree of genotoxic damage (i.e., residual genotoxic risk) in occupationally exposed subjects. The lymphocyte cytokinesis-block micronucleus (L-CBMN) assay is largely used for biological effect monitoring in subjects occupationally exposed to ANPD. In this study, we identified and analyzed the studies published reporting the use of the L-CBMN assay as biomarker of genotoxic risk in health care workers exposed to ANPD with the aim of performing meta-analysis and providing a meta-estimate of the genotoxic effect of exposure. We retrieved 24 studies, published from 1988 to 2015, measuring MN in peripheral blood lymphocytes in health care workers occupationally exposed to ANPD. In 15 out of the 24 studies (62.5%), increased MN frequencies were recognized in exposed subjects as compared to controls. The meta-analysis of MN frequency of the combined studies confirmed an association between occupational exposure to ANPD and cytogenetic effects with an overall meta-estimate of 1.67 [95% CI: 1.41-1.98]. In 16 out of the 24 studies (66.6%) at least one other genotoxicity biomarker, besides L-CBMN assay, was employed for biological effect monitoring. In several studies the effect of exposure to ANPD was evaluated also in terms of MN in exfoliated buccal cells. Other studies focused on genotoxicity endpoints, such as sister chromatid exchanges (3 studies), chromosome aberrations (6 studies), or primary DNA damage investigated by comet assay (7 studies). Overall, there was good agreement between other genotoxicity tests employed and L-CBMN assay outcomes.
Topics: Antineoplastic Agents; Cytokinesis; Humans; Lymphocytes; Micronucleus Tests; Occupational Exposure
PubMed: 27894689
DOI: 10.1016/j.mrrev.2016.05.001 -
International Journal of Occupational... Jan 2016Unintended occupational exposure to antineoplastic drugs (ANDs) may occur in medical personnel. Some ANDs are known human carcinogens and exposure can be monitored by... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Unintended occupational exposure to antineoplastic drugs (ANDs) may occur in medical personnel. Some ANDs are known human carcinogens and exposure can be monitored by genotoxic biomarkers.
OBJECTIVE
To evaluate the obstacles to obtaining conclusive results from a comet assay test to determine DNA damage among AND exposed healthcare workers.
METHODS
We systematically reviewed studies that used alkaline comet assay to determine the magnitude and significance of DNA damage among health care workers with potential AND exposure. Fifteen studies were eligible for review and 14 studies were used in the meta-analysis.
RESULTS
Under random effect assumption, the estimated standardized mean difference (SMD) in the DNA damage of health care workers was 1.93 (95% CI: 1.15-2.71, p < 0.0001). The resulting SMD was reduced to 1.756 (95% CI: 0.992-2.52, p < 0.0001) when the analysis only included nurses. In subgroup analyses based on gender and smoking, heterogeneity was observed. Only for studies reporting comet moment, I2 test results, as a measure of heterogeneity, dropped to zero. Heterogeneity analysis showed that date of study publication was a possible source of heterogeneity (B = -0.14; p < 0.0001).
CONCLUSIONS
A mixture of personal parameters, comet assay methodological variables, and exposure characteristics may be responsible for heterogenic data from comet assay studies and interfere with obtaining conclusive results. Lack of quantitative environmental exposure measures and variation in comet assay protocols across studies are important obstacles in generalization of results.
Topics: Antineoplastic Agents; Comet Assay; DNA Damage; Health Personnel; Humans; Mutagens; Occupational Exposure
PubMed: 27110842
DOI: 10.1080/10773525.2015.1123380