Percorrer por autor "Haveric, Anja"
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- The comet assay as a tool in human biomonitoring exposure to anaesthetic gases: a systematic review and meta-analysisPublication . Gajski, Goran; Haveric, Anja; Møller, Peter; Azqueta, Amaya; Giovannelli, Lisa; Gerić, Marko; Stopper, Helga; Bankoglu, Ezgi Eyluel; Collins, Andrew; Ladeira, CarinaAnaesthetic gases are agents used to induce and maintain general anaesthesia during surgical procedures. Common examples include sevoflurane, isoflurane, and desflurane, which act by depressing the central nervous system to produce unconsciousness and analgesia. These gases are administered through a vaporiser and inhaled via a mask or endotracheal tube. While effective, they can contribute to environmental pollution and increase the risk of occupational exposure. Medical personnel working in operating or post-operative facilities are unavoidably exposed to anaesthetic gases. Several adverse health effects have been associated with anaesthetic gas exposure; therefore, this review aims to summarise findings on DNA strand breaks, assessed by the comet assay in leucocytes of exposed medical workers. Standardised mean differences (SMDs) have been calculated by random effects models. The meta-analysis included 16 studies. Of these, 11 showed statistically significant increased levels of DNA strand breaks, whereas another five studies showed no significant effect. Overall, there is an increased level of DNA strand breaks in exposed subjects in unadjusted analysis (SMD = 1.17, 95 % confidence interval: 0.71, 1.62) as well as analysis adjusted for missing studies by the trim-and-fill method (SMD = 0.53, 95 % confidence interval: −0.14, 1.21). In conclusion, this systematic review and meta-analysis demonstrate that exposure to anaesthetic gases in an occupational setting induces primary DNA damage in human leucocytes, warranting further research to minimise any adverse effects on exposed medical personnel. Besides, the relevance of the use of the comet assay in assessing DNA damage in human biomonitoring studies is proven.
- The comet assay as a tool in human biomonitoring exposure to antineoplastic drugs: a systematic review and meta-analysisPublication . Ladeira, Carina; Azqueta, Amaya; Giovannelli, Lisa; Gajski, Goran; Gerić, Marko; Haveric, Anja; Stopper, Helga; Bankoglu, Ezgi Eyluel; Collins, Andrew; Møller, PeterAntineoplastic agents are toxic compounds, generally used in the treatment of cancers, which are recognized as carrying a cancer development risk. In this systematic review and meta-analysis of human biomonitoring studies, we have assessed the effects of exposure to antineoplastic drugs on levels of DNA strand breaks in leukocytes, measured by the comet assay. Focusing on the application of the comet assay in human biomonitoring of occupational exposure to antineoplastic agents, we have analyzed 458 original research studies that used this assay, following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA-ScR). The systematic review led to 23 studies, of which 20 studies met the criteria for inclusion in the meta-analysis. Using standardized mean difference and 95% confidence interval (CI), the meta-analyses show increased levels of DNA strand breaks in subjects exposed to antineoplastic drugs (1.26, 95% CI: 0.78, 1.73). Results originate mainly from studies on healthcare workers, with only one study in an industrial setting. Subgroup analysis indicates that all studies combined from middle-income countries have a higher effect size (1.77, 95% CI: 1.00, 2.55) than studies from high-income countries (0.49, 95% CI: 0.09, 0.90). This difference between middle- and high-income countries may be attributable in part to differences in exposure levels or exposure assessment. Additionally, sensitivity analysis indicates that studies with moderate/high risk of comet assay measurement bias have higher effect size (2.07, 95% CI: 0.82, 3.31) than studies with low risk of bias (0.73, 95% CI: 0.34, 1.13); and that studies with high risk of exposure misclassification have higher effect size (1.47, 95% CI: 0.89, 2.06) than studies with low/moderate risk (0.13, 955 CI: -0.08, 0.33). Most studies have a low/moderate risk of bias related to the comet assay procedure (15 out of 20 studies), absence of reporting the use of assay controls (1 out of 20 studies), blinded analysis of samples (7 out of 20 studies), and exposure assessment (16 out of 20 studies). In conclusion, this systematic review and meta-analysis show that exposure to antineoplastic drugs is associated with increased levels of DNA strand breaks in human leukocytes.
- The comet assay as a tool in human biomonitoring exposure to combustion-derived air pollution: a systematic review and meta-analysisPublication . Møller, Peter; Gajski, Goran; Gerić, Marko; Haveric, Anja; Stopper, Helga; Bankoglu, Ezgi Eyluel; Azqueta, Amaya; Giovannelli, Lisa; Collins, Andrew; Ladeira, CarinaHumans are exposed to environmental or occupational air pollution from combustion emissions in outdoor and indoor environments. Irrespective of the sources, combustion emissions are characterized by being a complex mixture of particles, volatile compounds and gases. The present systematic review summarizes results on DNA strand breaks measured by the comet assay in leukocytes, from studies on human exposure to traffic-related vehicle exhaust, biomass combustion and coke oven work environments. These exposures have in common the combustion of fuel, which generates particles and polycyclic aromatic hydrocarbons. Standardized mean differences (SMDs) have been calculated by random effects models. Meta-analyses show increased levels of DNA strand breaks in studies on traffic-related exhausts (SMD = 0.62, 95 % CI: 0.36, 0.89, n = 21), biomass combustion (1.73, 95 % CI: 0.72, 2.74, n = 10) and coke oven emission (0.84, 95 % CI: 0.30, 1.37, n = 10). Studies from high-income countries have reported much smaller differences in DNA strand break levels than have studies from middle-income countries. These differences may be attributed to higher exposures related to less strict emission control, and more susceptible populations in middle-income populations; unrecognized confounding despite efforts to match subjects on traditional confounders; or higher risk of comet assay measurement bias and exposure misclassification. In conclusion, this systematic review and meta-analysis show that exposure to combustion-derived air pollution, with clear exposure gradients in terms of particulate matter or polycyclic aromatic hydrocarbons, is associated with increased levels of DNA strand breaks in human leukocytes.
- The comet assay as a tool in human biomonitoring exposure to volatile organic compounds: a systematic review and meta-analysisPublication . Giovannelli, Lisa; Møller, Peter; Gajski, Goran; Stopper, Helga; Azqueta, Amaya; Bankoglu, Ezgi Eyluel; Haveric, Anja; Gerić, Marko; Collins, Andrew; Ladeira, CarinaExposure to volatile organic compounds (VOCs) such as benzene, styrene, toluene, and formaldehyde is associated with genotoxicity and increased risk of cancer. In this systematic review and meta-analysis, we have assessed the effects of VOCs exposure on levels of DNA strand breaks in leukocytes, measured by the comet assay, in human biomonitoring studies. The literature search led to 57 studies included in the review. Of these, 50 studies met the criteria to be used in the meta-analysis. Using standardized mean difference and 95 % confidence interval (CI), the meta-analyses show increased levels of DNA strand breaks in subjects exposed to benzene (1.59, 95 % CI: 0.94, 2.24), styrene (0.87, 95 % CI: 0.23, 1.51), formaldehyde (0.39, 95 % CI: −0.15, 0.92) and other organic solvents (2.14, 95 % CI: 1.48, 2.81). Results originate mainly from studies on workers, with only a few studies on environmental benzene exposure. Subgroup analysis indicates that all studies combined from middle-income countries have a higher effect size (1.81, 95 % CI: 1.26, 2.36, n = 28) than studies from high-income countries (0.87, 95 % CI: 0.49, 1.24, n = 22). This difference between middle- and high-income countries may be due to differences in exposure levels or exposure assessment. However, this might not be the only reason, as sensitivity analysis indicates that effect sizes are at risk of comet assay measurement bias, as 78 % (39 out of 50 studies) and 60 % (30 studies) have not reported the use of assay controls and blinded analysis of samples, respectively. Relatively few studies have a high risk of bias due to an inadequate comet assay procedure description (14 %, 7 studies) and exposure misclassification (16 %, 8 studies). Limitations of the study were the differences in protocols, comet descriptors, exposure assessment, and control for confounding factors among the studies. In conclusion, this systematic review and meta-analysis show that exposure to VOCs – benzene, styrene, formaldehyde, and others – is associated with increased levels of DNA strand breaks in human leukocytes.
- The comet assay as a tool in human biomonitoring of exposure to heavy metals: a systematic review and meta-analysisPublication . Møller, Peter; Bankoglu, Ezgi Eyluel; Stopper, Helga; Gajski, Goran; Gerić, Marko; Haveric, Anja; Azqueta, Amaya; Giovannelli, Lisa; Collins, Andrew; Ladeira, CarinaExposure to heavy metals such as lead, arsenic, and chromium is associated with genotoxicity and increased risk of cancer. In this systematic review and meta-analysis, we have assessed the effects of heavy metal exposure on levels of DNA strand breaks in leukocytes, measured by the comet assay, in human biomonitoring studies. We distinguish between traditional toxic metals (lead), semi-metals/metalloids (arsenic), transition metals (chromium), and other heavy metals. The literature search led to 66 studies, which were assessed by meta-analysis. Using standardized mean difference and 95 % confidence interval (CI), the meta-analyses show increased levels of DNA strand breaks in subjects exposed to lead (1.99, 95 % CI: 1.47, 2.51), arsenic (1.36, 95 % CI: 0.94, 1.77), chromium/welding fume (2.03, 95 % CI: 1.48, 2.57), and other heavy metals (0.81, 95 % CI: 0.45, 1.18). Subgroup analysis indicates that all studies combined from middle-income countries have a higher effect size (1.99, 95 % CI: 1.63, 2.35) than studies from high-income countries (0.81, 95 % CI: 0.37, 1.26). The lower effect size in high-income countries may be due to differences in exposure levels, related to stricter regulation of emissions or more awareness/use of personal protective equipment in the working environment. Sensitivity analysis does not unequivocally link effect size to comet assay measurement bias, inferred by insufficient information on comet assay procedures, missing assay controls, non-blinded analysis of samples, or exposure misclassification. In conclusion, this systematic review and meta-analysis shows that exposure to heavy metals - lead, arsenic, and chromium - is associated with increased levels of DNA strand breaks in human leukocytes.
- The comet assay as a tool in human biomonitoring studies: effects of confounding factorsPublication . Møller, Peter; Gajski, Goran; Gerić, Marko; Giovannelli, Lisa; Azqueta, Amaya; Haveric, Anja; Stopper, Helga; Bankoglu, Ezgi Eyluel; Collins, Andrew; Ladeira, CarinaThe comet assay is widely used in human biomonitoring studies of environmental and occupational exposures. However, it is clear from multiple studies that various types of confounding factors might affect the direct relationship between exposure and DNA damage in the comet assay. In addition to common confounders such as age, sex, and smoking, other factors considered to be important determinants for background levels of DNA damage in the comet assay include exhaustive physical exercise, chronic diseases, medical treatment, and diet. These are typically controlled in biomonitoring studies by restriction or matching of subjects. Period effects (or seasonal variation) have been observed in a relatively large number of studies. There are various putative factors, which may cause period effects, including temporal variation in solar radiation, temperature, and air pollution. The present review describes the effects of these confounding factors in measurements of DNA strand breaks by the comet assay. In general, the literature does not indicate that any confounding factor is consistently associated with an increased level of DNA damage, measured by the comet assay. In this respect, it is important to balance the need to control for confounding with the risk of introducing in the statistical analysis a variable, which is influenced by exposure and outcome (i.e. collider bias). In addition, it is important that investigators describe procedures for controlling the effect of confounding factors in the selection of subjects and statistical analysis. Care should be taken in study design and statistical analysis to avoid unwanted effects of confounding factors.
- The comet assay as a tool in human biomonitoring studies of environmental and occupational exposure to chemicals: a systematic scoping reviewPublication . Ladeira, Carina; Møller, Peter; Giovannelli, Lisa; Gajski, Goran; Haveric, Anja; Bankoglu, Ezgi Eyluel; Azqueta, Amaya; Gerić, Marko; Stopper, Helga; Cabêda, José; Tonin, Fernanda; Collins, AndrewBiomonitoring of human populations exposed to chemical substances that can act as potential mutagens or carcinogens may enable the detection of damage and early disease prevention. In recent years, the comet assay has become an important tool for assessing DNA damage, both in environmental and occupational exposure contexts. To evidence the role of the comet assay in human biomonitoring, we have analysed original research studies of environmental or occupational exposure that used the comet assay in their assessments, following the PRISMA-ScR method (preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews). Groups of chemicals were designated according to a broad classification, and the results obtained from over 300 original studies (n = 123 on air pollutants, n = 14 on anaesthetics, n = 18 on antineoplastic drugs, n = 57 on heavy metals, n = 59 on pesticides, and n = 49 on solvents) showed overall higher values of DNA strand breaks in the exposed subjects in comparison with the unexposed. In summary, our systematic scoping review strengthens the relevance of the use of the comet assay in assessing DNA damage in human biomonitoring studies.