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.

Coronary artery disease (CAD) is the leading cause of morbidity and mortality worldwide. Coronary angiography allows an accurate assessment of the extent and severity of atherosclerotic coronary narrowing, but it provides little characterization of early detection of potentially asymptomatic vulnerable plaque. The identification of the coronary \"vulnerable patient\" or high-risk plaques remains a major challenge in the treatment of CAD. Recently, growing evidence shows that DNA damage plays a role in the initiation and progression of atherosclerotic plaque. Cytokinesis-block micronucleus (CBMN) assay is one of the most frequently used and validated method for assessing chromosomal damage and genetic instability. Accordingly, the purpose of this systematic review was to retrieve and discuss existing literature on the studies assessing the association between MN and angiographically-proven CAD. A total of 8 studies published between 2001 and 2017 were included in the meta-analysis. Despite a large heterogeneity between studies (I2= 99.7 %, p < 0.0001), an overall increase of MN frequencies was found in patients with CAD compared with control group (meta-MR = 1.96; 95 % CI, 1.5-3.2, p = 0.009). A subgroup analysis showed an increase in the frequency of MN formation for both two- vessel (MR = 2.13, 95 % CI: 0.9-6.9, p = 0.08) and three-vessel disease (MR = 2.89, 95 % CI: 1.84-4.55, P = 0.06). Overall, the results of this meta-analysis provide evidence of an association between CBMN and presence, extent and severity of angiographically-assessed CAD. However, the small number of papers analyzed requires further large and more rigorously designed studies, carefully considering a series of clinical confounding factors, such as the quality of the metabolic control, the influence of drugs and radiation imaging treatments.

About 40 million workers are occupationally exposed to crystalline silica (CS) which was classified as a human carcinogen by the IARC. It is assumed that damage of the genetic material via inflammation and reactive oxygen species by CS lead to formation of malignant cells. We conducted a systematic literature search to find out if inhalation of CS containing dusts at workplaces causes damage of the genetic material. Thirteen studies were found eligible for this review, in most of them (n = 9) micronuclei (MN) which reflect structural/numerical chromosomal aberrations were monitored in lymphocytes and/or in exfoliated buccal cells. In 5 investigations DNA damage was measured in blood cells in single cell gel electrophoresis (comet) experiments. Frequently studied groups were potters, stone cutters, miners and construction workers. Results of meta-analyses show that exposure to CS causes formation of MN and DNA breaks, the overall ratio values were in exposed workers 2.06- and 1.96-fold higher than in controls, respectively. Two studies reported increased levels of oxidized guanine, and higher levels of DNA adducts with malondialdehyde indicating that exposure to CS leads to oxidative damage. The exposure of the workers to CS was quantified only in two studies, information concerning the size and chemical structures of the particles is lacking in most investigations. Therefore, it is not possible to use the results to derive occupational exposure limits of workers to CS which vary strongly in different countries. Nevertheless, the evaluation of the current state of knowledge shows that biomonitoring studies in which damage of the genetic material is measured in CS exposed workers can contribute to assess adverse health effects as consequence of DNA instability in specific occupations.

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; I2 = 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.

Human exposure to (certain forms of) crystalline silica (CS) potentially results in adverse effects on human health. Since 1997 IARC has classified CS as a Group 1 carcinogen [1], which was confirmed in a later review in 2012 [2]. The genotoxic potential and mode of genotoxic action of CS was not conclusive in either of the IARC reviews, although a proposal for mode of actions was made in an extensive review of the genotoxicity of CS by Borm, Tran and Donaldson in 2011 [3]. The present study identified 141 new papers from search strings related to genotoxicity of respirable CS (RCS) since 2011 and, of these, 17 relevant publications with genotoxicity data were included in this detailed review.Studies on in vitro genotoxic endpoints primarily included micronucleus (MN) frequency and % fragmented DNA as measured in the comet assay, and were mostly negative, apart from two studies using primary or cultured macrophages. In vivo studies confirmed the role of persistent inflammation due to quartz surface toxicity leading to anti-oxidant responses in mice and rats, but DNA damage was only seen in rats. The role of surface characteristics was strengthened by in vitro and in vivo studies using aluminium or hydrophobic treatment to quench the silanol groups on the CS surface.In conclusion, the different modes of action of RCS-induced genotoxicity have been evaluated in a series of independent, adequate studies since 2011. Earlier conclusions on the role of inflammation driven by quartz surface in genotoxic and carcinogenic effects after inhalation are confirmed and findings support a practical threshold. Whereas classic in vitro genotoxicity studies confirm an earlier no-observed effect level (NOEL) in cell cultures of 60-70 μg/cm2, transformation frequency in SHE cells suggests a lower threshold around 5 μg/cm2. Both levels are only achieved in vivo at doses (2-4 mg) beyond in vivo doses (> 200 μg) that cause persistent inflammation and tissue remodelling in the rat lung.

Colorectal cancer (CRC) is among the most common cancers. In fact, it is placed in the third place among the most diagnosed cancer in men, after lung and prostate cancer, and in the second one for the most diagnosed cancer in women, following breast cancer. Moreover, its high mortality rates classifies it among the leading causes of cancer‑related death worldwide. Thus, in order to help clinicians to optimize their practice, it is crucial to introduce more effective tools that will improve not only early diagnosis, but also prediction of the most likely progression of the disease and response to chemotherapy. In that way, they will be able to decrease both morbidity and mortality of their patients. In accordance with that, colon cancer research has described numerous biomarkers for diagnostic, prognostic and predictive purposes that either alone or as part of a panel would help improve patient\'s clinical management. This review aims to describe the most accepted biomarkers among those proposed for use in CRC divided based on the clinical specimen that is examined (tissue, faeces or blood) along with their restrictions. Lastly, new insight in CRC monitoring will be discussed presenting promising emerging biomarkers (telomerase activity, telomere length and micronuclei frequency).

OBJECTIVE: Anesthetic gases have been used for a long time. Adverse effects of anesthetic gases to occupationally exposed people have been well documented in the literature. Due to low solubility, these gases are rapidly eliminated from the human body. Nevertheless, neurotoxic, immunosuppressive, hepatotoxic and reproductive toxicological effects have been shown in many of the scientific works. However, there is no detailed systematic bio-monitoring review about genotoxicity risk among occupationally exposed people. We herein performed systematic review based on relevant studies.
METHODS: This work reviews the published literature about the genotoxic effects of anesthetic gases among operating room personnel published between 1989 and September 2015. We performed a computerized search of articles on Pubmed, Scopus, Web of Science, and Google Scholar.
RESULTS: Analyzed works have shown us that chromosomal aberration, sister chromatid exchanges, micronucleus and comet assays were the most frequently used genotoxicity end-points. In almost all data, occupational exposure to anesthetic gases has been associated with statistically significant increase in genotoxic damage among operating room personnel.
CONCLUSIONS: Health care workers are exposed to wide variety of agents including biological, physical and chemical factors. Among them anesthetic gases seems to be deserve special attentions since their genotoxic, mutagenic activities. In addition, chronic exposure to all anesthetic gases instead of alone induces cumulative genotoxic effects.

Glyphosate-based herbicides are among the most used pesticides worldwide. Reviews on the safety of glyphosate have been conducted by several regulatory agencies and researches centers, many times with contradictory results. This study is a systematic meta-analytical review of experimental studies on the relationship between exposure to the glyphosate (GLY) and its formulations with the formation of micronuclei (MN) to establish a quantitative estimate of the environmental risks. The natural logarithm (ln) of the estimated response ratio was calculated from 81 experiments. A meta-analysis was performed on the complete data set, and individual meta-analyses were conducted after stratification by test system, class of vertebrate, exposure route, gender, endpoints, type of literature, formulation, GLY dose and exposure time. A forest plot showed an overall positive association between GLY exposure and its formulations and MN, corroborated by the cumulative effects size. Different responses were observed on mammalian and non-mammalian. Interesting results was noticed in exposure route where oral administration of GLY presented no significance. Exposure by intraperitoneal injection presented the highest MN formation. Pure GLY caused fewer effects than to commercial mixtures, but both presented mutagenic effects. The studies with males presented significant responses, while studies with females were not significant. The cumulative effects size was not clearly related to GLY dose, and was negatively related to exposure time. It can be attributed to different test systems, exposure routes and protocols analyzed. In conclusion, our results support the hypothesis that exposure to GLY and its formulations increases the frequency of MN formation.

The association between ambient air pollution exposure and lung cancer risk has been investigated in prospective studies and the results are generally consistent, indicating that long-term exposure to air pollution may cause lung cancer. Despite the prospective nature and consistent findings of these studies, causality assessment can benefit from biomarker research. In the present systematic review, we assess the contribution of intermediate biomarkers in epidemiological studies, to ascertain whether their measurement reinforces causal reasoning. We have reviewed 524 papers which described the relationships between ambient air pollution and biological markers of dose and early response. The evidence for each marker was evaluated using assessment criteria which rate a group of studies from A (strong) to C (weak) on amount of evidence, replication of findings, and protection from bias. Biomarkers that scored A or B for all three criteria are included here. The markers that fulfilled the inclusion criteria are: 1-hydroxypyrene, DNA adducts, chromosomal aberrations, micronuclei, oxidative damage to nucleobases, and methylation changes. These biomarkers cover the whole spectrum of disease onset and progression from external exposure to tumour formation and some have also been suggested as risk predictors of future cancer, reinforcing causal reasoning. However, methodological issues such as confounding, publication bias and use of surrogate tissues instead of target tissues in studies on these markers are of concern. The identified biological markers have potential to shed light on the pathways of carcinogenesis, thus defining the association more clearly for public health interventions.

Harmful effects of oil spills on diverse flora and fauna species have been extensively studied. Nevertheless, only a few studies have been compiled in the literature dealing with the repercussions of oil exposure on human health; most of them have focused on acute effects and psychological symptoms. The objective of this work was to gather all these studies and to analyze the possible consequences of this kind of complex exposure in the different aspects of human health. Studies found on this topic were related to the disasters of the Exxon Valdez, Braer, Sea Empress, Nakhodka, Erika, Prestige and Tasman Spirit oil tankers. The majority of them were cross-sectional; many did not include control groups. Acute effects were evaluated taking into account vegetative-nervous symptoms, skin and mucous irritations, and also psychological effects. Genotoxic damage and endocrine alterations were assessed only in individuals exposed to oil from Prestige. The results of the reviewed articles clearly support the need for biomonitoring human populations exposed to spilled oils, especially those individuals involved in the cleanup, in order to evaluate not only the possible immediate consequences for their health but also the medium- and long-term effects, and the effectiveness of the protective devices used.