This study aims to identify factors possibly contributing to complications in children with acute leukaemia. Despite diverse etiological causes, similar processes trigger the process of cell malignancy. Genomic instability has received considerable attention in this context.

We conducted chromosomal analysis of bone marrow cells and measured the micronuclei (Mn) level in buccal cells over time. Statistical reliability assessment was performed using Analysis of variance (ANOVA), and the data were analyzed and visualized using the SPSS 12 statistical analysis software package.

On the 15th day of treatment, our findings confirmed a statistically significant correlation (χ2=3.88, P=0.04) between the number of blasts in the bone marrow and unfavourable outcome in patients with a near-tetraploid chromosome clone. Additionally, on the 33rd day of treatment, we observed a correlation between an elevated number of Mn and relapses.

While it is commonly believed that a hyperdiploid clone with >50 chromosomes in childhood acute lymphoblastic leukaemia confers favorable outcome, our study revealed partially heterogeneous results and poor prognosis in patients with a near-tetraploid clone. We have also identified a correlation between the Mn level on the 33rd day of treatment and the development of complications. It is possible that the increased Mn values and the occurrence of relapses were influenced by the individual patient's sensitivity to the genotoxic effect of the medication.

Hexavalent chromium (Cr(VI)) is a carcinogen. Exposure to Cr(VI) may occur in different industrial processes such as chrome plating and stainless steel welding. The aim of this study was to assess occupational exposure to Cr(VI) in Denmark.

This cross-sectional study included 28 workers and 8 apprentices with potential Cr(VI) exposure and 24 within company controls, all recruited from six companies and one vocational school. Use of occupational safety and health (OSH) risk prevention measures were assessed through triangulation of interviews, a questionnaire and systematic observations. Inhalable Cr(VI) and Cr-total were assessed by personal air exposure measurements on Cr(VI) exposed participants and stationary measurements. Cr concentrations were measured in urine and in red blood cells (RBC) (the latter reflecting Cr(VI)). Genotoxicity was assessed by measurement of micronuclei in peripheral blood reticulocytes (MNRET).

At announced visits, a consistent high degree of compliance to OSH risk prevention measures were seen in 'chromium bath plating' for both technical devices (e.g. ventilation, plastic balls, sheet coverings) and in the use of personal protective equipment (e.g. gloves, respirators), yet a lesser degree of compliance was observed in 'stainless steel welding'. The geometric mean of the air concentration of Cr(VI) was 0.26 μg/m3 (95% confidence interval (CI): 0.12-0.57) for the Cr(VI)-exposed workers and 3.69 μg/m3 (95% CI: 1.47-9.25) for the Cr(VI)-exposed apprentices. Subdivided by company type, the exposure levels were 0.13 μg/m3 (95% CI: 0.04-0.41) for companies manufacturing and processing metal products, and 0.81 μg/m3 (95% CI: 0.46-1.40) for bath plating companies. Workers with occupational exposure to Cr(VI) had significantly higher median levels of urinary Cr (2.42 μg/L, 5th-95th percentile 0.28-58.39), Cr in RBC (0.89 μg/L, 0.54-4.92) and MNRET (1.59 ‰, 0.78-10.92) compared to the within company controls (urinary: 0.40 μg/L, 0.16-21.3, RBC: 0.60 μg/L, 0.50-0.93,MNRET: 1.06 ‰, 0.71-2.06). When sub-dividing by company type, urinary Cr (4.61 μg/L, 1.72-69.5), Cr in RBC (1.33 μg/L, 0.95-4.98) and MNRET (1.89 μg/L, 0.78-12.92) levels were increased for workers with potential Cr(VI) exposure in bath-plating companies, and when subdividing by work task, workers engaged in process operation had increased levels of urinary Cr (8.51 μg/L, 1.71-69.5), Cr in RBC (1.33 μg/L, 0.95-4.98) and MNRET (1.89 μg/L, 0.82-12.92) levels.

This biomonitoring study shows that bath platers were highly exposed to Cr(VI), as suggested by relatively high levels of urinary Cr, Cr in RBC and increased levels of micronuclei. The urinary Cr concentrations were high when compared to the French biological limit value of 2.5 μg Cr/L, corresponding to the Danish occupational exposure limit of 1 μg/m3. This, in turn, indirectly suggests that additional exposure routes than via air may contribute to the exposure. For welders, no statistically significant increases compared to within company controls were observed, however, the observed urinary Cr levels were similar to the levels observed in a European study (HBM4EU), and were higher than the levels observed for welders in Sweden (SafeChrom). In spite of a high degree of self-reported and observed compliance to OSH risk prevention measures during announced visits, the biomarkers of exposure reflecting recent exposure (urinary Cr) or exposure during the last four months (Cr in RBC) may point to variation in compliance to OSH risk prevention measures in general. Reduced occupational exposure to Cr(VI) may be achieved by applying the hierarchy of controls in eliminating or substituting Cr(VI), and the use of more effective technical solutions (e.g. automation).

In this study, we used the cytokinesis-block micronucleus (CBMN) assay to evaluate the background frequency of cytogenetic damage in peripheral blood lymphocytes of the general population concerning different anthropometric data and lifestyle factors. The background frequency of CBMN assay parameters was analysed in 850 healthy, occupationally non-exposed male and female subjects (average age, 38±11 years) gathered from the general Croatian population from 2000 to 2023. The mean background values for micronuclei (MNi) in the whole population were 5.3±4.3 per 1000 binucleated cells, while the mean frequency of nucleoplasmic bridges (NPBs) was 0.7±1.3 and of nuclear buds (NBUDs) 3.1±3.2. The cut-off value, which corresponds to the 95th percentile of the distribution of 850 individual values, was 14 MNi, 3 NPBs, and 9 NBUDs. Results from our database also showed an association of the tested genomic instability parameters with age and sex but also with other lifestyle factors. These findings underscore the importance of considering several anthropometric and lifestyle factors when conducting biomonitoring studies. Overall, the normal and cut-off values attained here present normal values for the general population that can later serve as baseline values for further human biomonitoring studies either in Croatia or worldwide.

Patients with arterial hypertension have an increased risk of developing tumors, particularly renal cell carcinoma. Arterial hypertension is linked to DNA damage via the generation of oxidative stress, in which an upregulated renin-angiotensin-aldosterone system plays a crucial role. The current study investigated surrogates of oxidative stress and DNA damage in a group of hypertensive patients (HypAll, n = 64) and subgroups of well (HypWell, n = 36) and poorly (HypPoor, n = 28) controlled hypertensive patients compared to healthy controls (n = 8). In addition, a longitudinal analysis was performed with some of the hypertensive patients. Markers for oxidative stress in plasma (SHp, D-ROM, and 3-nitrotyrosine) and urine (8-oxodG, 15-F2t-isoprostane, and malondialdehyde) and markers for DNA damage in lymphocytes (γ-H2AX and micronuclei) were measured. In HypAll, all markers of oxidative stress except malondialdehyde were increased compared to the controls. After adjustment for age, this association was maintained for the protein stress markers SHp and 3-nitrotyrosine. With regard to the markers for DNA damage, there was no difference between HypAll and the controls. Further, no significant differences became apparent in the levels of both oxidative stress and DNA damage between HypWell and HypPoor. Finally, a positive correlation between the development of blood pressure and oxidative stress was observed in the longitudinal study based on the changes in D-ROM and systolic blood pressure. In conclusion, we found increased oxidative stress in extensively treated hypertensive patients correlating with the level of blood-pressure control but no association with DNA damage.

Accumulation of deoxyribonucleic acid (DNA) damage diminishes cellular health, increases risk of developmental and degenerative diseases, and accelerates aging. Optimizing nutrient intake can minimize accrual of DNA damage. The objectives of this review are to: 1) assemble and systematically analyze high-level evidence for the effect of supplementation with micronutrients and phytochemicals on baseline levels of DNA damage in humans, and 2) use this knowledge to identify which of these essential micronutrients or nonessential phytochemicals promote DNA integrity in vivo in humans. We conducted systematic literature searches of the PubMed database to identify interventional, prospective, cross-sectional, or in vitro studies that explored the association between nutrients and established biomarkers of DNA damage associated with developmental and degenerative disease risk. Biomarkers included lymphocyte chromosome aberrations, lymphocyte and buccal cell micronuclei, DNA methylation, lymphocyte/leukocyte DNA strand breaks, DNA oxidation, telomere length, telomerase activity, and mitochondrial DNA mutations. Only randomized, controlled interventions and uncontrolled longitudinal intervention studies conducted in humans were selected for evaluation and data extraction. These studies were ranked for the quality of their study design. In all, 96 of the 124 articles identified reported studies that achieved a quality assessment score ≥ 5 (from a maximum score of 7) and were included in the final review. Based on these studies, nutrients associated with protective effects included vitamin A and its precursor β-carotene, vitamins C, E, B1, B12, folate, minerals selenium and zinc, and phytochemicals such as curcumin (with piperine), lycopene, and proanthocyanidins. These findings highlight the importance of nutrients involved in (i) DNA metabolism and repair (folate, vitamin B12, and zinc) and (ii) prevention of oxidative stress and inflammation (vitamins A, C, E, lycopene, curcumin, proanthocyanidins, selenium, and zinc). Supplementation with certain micronutrients and their combinations may reduce DNA damage and promote cellular health by improving the maintenance of genome integrity.

Hyperoside is a flavonol glycoside isolated from various plant genera such as Hypericum and Crataegus. It has an important place in the human diet and is used medically to relieve pain and ameliorate cardiovascular functions. However, a comprehensive profile of the genotoxic and antigenotoxic effects of hyperoside is not known. The current study aimed to investigate the genotoxic and antigenotoxic effects of hyperoside against genetic damages induced by two genotoxins (MMC and H₂O₂) in human lymphocytes using chromosomal aberrations (CAs), sister chromatid exchanges (SCEs), and micronucleus (MN) assays in human peripheral blood lymphocytes in vitro. Blood lymphocytes were incubated with 7.8-62.5 μg/mL concentrations of hyperoside alone and simultaneously with 0.20 μg/mL Mitomycin C (MMC) or 100 μM Hydrogen peroxide (H₂O₂). Hyperoside did not exhibit genotoxic potential in the CA, SCE, and MN assays. Moreover, it did not cause a decrease in mitotic index (MI) which is an indicator of cytotoxicity. On the other hand, hyperoside significantly decreased CA, SCE, and MN (except for MMC treatment) frequencies induced by MMC and H₂O₂. Hyperoside, increased mitotic index against both mutagenic agents at 24-h treatment when compared to positive control. Our results demonstrate that hyperoside exhibited antigenotoxic effects rather than genotoxic in vitro human lymphocytes. Therefore, hyperoside may be a potential preventive agent in inhibiting chromosomal and oxidative damage induced by genotoxic chemicals.

New development and optimization of oncologic strategies are steadily increasing the number of long-term cancer survivors being at risk of developing second primary neoplasms (SPNs) as a late consequence of genotoxic cancer therapies with the highest risk among former childhood cancer patients. Since risk factors and predictive biomarkers for therapy-associated SPN remain unknown, we examined the sensitivity to mild replication stress as a driver of genomic instability and carcinogenesis in fibroblasts from 23 long-term survivors of a pediatric first primary neoplasm (FPN), 22 patients with the same FPN and a subsequent SPN, and 22 controls with no neoplasm (NN) using the cytokinesis-block micronucleus (CBMN) assay. Mild replication stress was induced with the DNA-polymerase inhibitor aphidicolin (APH). Fibroblasts from patients with the DNA repair deficiency syndromes Bloom, Seckel, and Fanconi anemia served as positive controls and for validation of the CBMN assay supplemented by analysis of chromosomal aberrations, DNA repair foci (γH2AX/53BP1), and cell cycle regulation. APH treatment resulted in G2/M arrest and underestimation of cytogenetic damage beyond G2, which could be overcome by inhibition of Chk1. Basal micronuclei were significantly increased in DNA repair deficiency syndromes but comparable between NN, FPN, and SPN donors. After APH-induced replication stress, the average yield of micronuclei was significantly elevated in SPN donors compared to FPN (p = 0.013) as well as NN (p = 0.03) donors but substantially lower than for DNA repair deficiency syndromes. Our findings suggest that mild impairment of the response to replication stress induced by genotoxic impacts of DNA-damaging cancer therapies promotes genomic instability in a subset of long-term cancer survivors and may drive the development of an SPN. Our study provides a basis for detailed mechanistic studies as well as predictive bioassays for clinical surveillance, to identify cancer patients at high risk for SPNs at first diagnosis.

Oil exploitation, drilling, transportation, and processing in refineries produces a complex mixture of chemical compounds, including polycyclic aromatic hydrocarbons (PAHs), which may affect the health of populations living in the zone of influence of mining activities (PZOI). Thus, to better understand the effects of oil exploitation activities on cytogenetic endpoint frequency, we conducted a biomonitoring study in the Hitnü indigenous populations from eastern Colombia by using the cytokinesis micronucleus cytome assay (CBMN-cyt). PAH exposure was also measured by determine urine 1-hydroxypyrene (1-OHP) using HPLC. We also evaluated the relationship between DNA damage and 1-OHP levels in the oil exploitation area, as well as the modulating effects of community health factors, such as Chagas infection; nutritional status; and consumption of traditional hallucinogens, tobacco, and wine from traditional palms. The frequencies of the CBMN-cyt assay parameters were comparable between PZOI and Hitnü populations outside the zone of influence of mining activities (POZOI); however, a non-significant incremental trend among individuals from the PZOI for most of the DNA damage parameters was also observed. In agreement with these observations, levels of 1-OHP were also identified as a risk factor for increased MN frequency (PR = 1.20) compared to POZOI (PR = 0.7). Proximity to oil exploitation areas also constituted a risk factor for elevated frequencies of nucleoplasmic bridges (NPBs) and APOP-type cell death. Our results suggest that genetic instability and its potential effects among Hitnü individuals from PZOI and POZOI could be modulated by the combination of multiple factors, including the levels of 1-OHP in urine, malnutrition, and some traditional consumption practices.

The systematic review (SR) with meta-analysis aimed to infer if micronucleus assay using oral mucosal cells a useful biomarker for biomonitoring populations continuously exposed to pesticides (EP). The SR has been made in accordance with the PRISMA-P guidelines. The PICOS strategy has focused to answer the following question: "Does exposure to pesticides cause genetic damage in oral cells?" The literature search was made in the following scientific databases: Web of Science, PubMed/Medline, and Scopus. The approach was defined as follows: standardized mean difference (SMD) and 95% confidence intervals (CI). The quality assessment of manuscripts was obtained by the EPHPP (Effective Public Health Practice Project). The GRADE tool was chosen for assessing the quality of evidence. A total of 108 articles were selected in this setting. After screening abstracts and titles, 23 manuscripts were evaluated for eligibility. After reviewing the studies, two were considered weak and 22 were classified as moderate or strong. The meta-analysis data pointed out statistically significant differences in volunteers exposed to EP (SMD = 1.23, 95% CI, 0.69 to 1.77, p < 0.001), with a Tau2 = 1.44; Chi2 = 566.38, and p < 0.001, so that the selected manuscripts were considered heterogeneous and the I2 of 97% indicated high heterogeneity. Taken together, this review was able to validate the micronucleus assay in oral exfoliated cells as a useful biomarker in individuals continuously exposed to EP because the studies categorized as moderate and strong have demonstrated positive response related to mutagenesis.

The purpose of the "Micronuclei and Disease" special issue (SI) is to: (i) Determine the level of evidence for association of micronuclei (MN), a biomarker of numerical and structural chromosomal aberrations, with risk of specific diseases in humans; (ii) Define plausible mechanisms that explain association of MN with each disease; (iii) Identify knowledge gaps and research needed to translate MN assays into clinical practice. The "MN and Disease" SI includes 14 papers. The first is a review of mechanisms of MN formation and their consequences in humans. 11 papers are systematic reviews and/or meta-analyses of the association of MN with reproduction, child health, inflammation, auto-immune disease, glycation, metabolic diseases, chronic kidney disease, cardiovascular disease, eleven common cancers, ageing and frailty. The penultimate paper focuses on effect of interventions on MN frequency in the elderly. A road map for translation of MN data into clinical practice is the topic of the final paper. The majority of reviewed studies were case-control studies in which the ratio of mean MN frequency in disease cases relative to controls, i.e. the mean ratio (MR), was calculated. The mean of these MR values, estimated by meta-analyses, for lymphocyte and buccal cell MN in non-cancer diseases were 2.3 and 3.6 respectively, and for cancers they were 1.7 and 2.6 respectively. The highest MR values were observed in studies of cancer cases in which MN were measured in the same tissue as the tumour (MR = 4.9-10.8). This special issue is an important milestone in the evidence supporting MN as a reliable genomic biomarker of developmental and degenerative disease risk. These advances, together with results from prospective cohort studies, are helping to identify diseases in which MN assays can be practically employed in the clinical setting to better identify high risk patients and to prioritise them for preventive therapy.