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Anti-proliferative effects of halogenated boroxine – K2(B3O3F4OH) (HB) – have been confirmed in multiple cancer cell lines, including melanoma, but the exact mechanism of action is still unknown. This study aimed to determine its cytotoxic effects on human Caucasian melanoma (GR-M) cell growth in vitro as well as on the expression of cell death-related genes BCL-2, BECN1, DRAM1, and SQSTM1. GR-M and peripheral blood mononuclear (PBM) cells were treated with different HB concentrations and their growth inhibition and relative gene expression profiles were determined using the Alamar blue assay and real-time PCR. HB significantly inhibited cell growth of both GR-M and PBM cells but was even more effective in GR-M melanoma cells, as significant inhibition occurred at a lower HB concentration of 0.2 mg/mL. GR-M BCL-2 expression was significantly downregulated (P=0.001) at HB concentration of 0.4 mg/mL, which suggests that HB is a potent tumour growth inhibitor. At the same time, it upregulated BCL-2 expression in normal (PBM) cells, probably by activating protective mechanisms against induced cytotoxicity. In addition, all but the lowest HB concentrations significantly upregulated SQSTM1 (P=0.001) in GR-M cells. Upregulated BECN1 expression suggests early activation of autophagy at the lowest HB concentration in SQSTM1 cells and at all HB concentrations in PBM cells. Our findings clearly show HB-associated cell death and, along with previous cytotoxicity studies, reveal its promising anti-tumour potential.

Twelve previously synthesized, biologically active 2,6,7-trihydroxyxanthen-3-one derivatives were evaluated in vitro for antiproliferative activity. Compounds were screened against HeLa, SW620, HepG2 and A549 tumor cell lines. Compound with the trifluormethyl group on C-4’ position of the phenyl ring showed the best inhibitory activity towards HeLa and A549 tumor cells with IC50 of 0.7 and 4.1 µmol L−1, resp. Compound with chlorine and fluorine substituents on aryl ring showed the best antiproliferative activity against SW620 with IC50 of 4.1 µmol L–1 and against HepG2 tumor cell line with IC50 of 4.2 µmol L–1. Analyses of cytotoxic and genotoxic potential of the trifluormethyl derivative were performed with cytokinesis-block micronucleus cytome assay in human lymphocyte culture and revealed no genotoxic and cytotoxic effects. The most potent compounds were subjected to molecular docking simulations in order to analyse bindings to molecular targets and, at the same time, further support the results of experimental cytotoxic tests. Docking studies showed sites of importance in forming hydrogen bonds of the most potent compounds with targets of interest.

Background: Waterpipe, also known as a hookah or narghile, is a type of tobacco products consumption device. Recently it has been increasingly popular in Bosnia and Herzegovina and the region. Waterpipe consumers are predominantly adolescents and young adults. Many of them believe in slighter harmful effects of waterpipes, compared to cigarettes. We aimed to determine the DNA damage in oral leukocytes and buccal cells of young individuals who have smoked a waterpipe for more than one year., Methods: The study group consisted of 40 cigarette non-smokers who regularly smoked a waterpipe on average of once per week. As a control, 40 non-smoking individuals were selected to match smokers for age. All participants in the study were healthy male and female adults from Bosnia and Herzegovina, 18-30 years of age. Before sampling, detailed survey and informed consent have been provided by each participant. Comet assay in oral leukocytes and buccal micronucleus cytome (BMCyt) assay in exfoliated buccal cells were applied., Results: Almost half of waterpipe smokers (WPS) tasted waterpipe at 15-16 years of age. Comet assay analysis showed increased tail intensity, tail length, and tail moment values among WPS compared to non-smokers (NS) (p = 0.0001, p = 0.0067, and p = 0.0001, respectively). Frequencies of the micronucleated (p = 0.0004), binucleated (p = 0.01), karyorrhectic, (p = 0.0036), and pycnotic cells (p = 0.03) were significantly higher in WPS compared to NS group., Conclusions: Genotoxicity and DNA damage biomarkers were increased in oral leukocytes and exfoliated buccal cells of young waterpipe smokers from Bosnia and Herzegovina, compared to NS group., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 University of Sarajevo - Institute for Genetic Engineering and Biotechnology. Published by Elsevier Ltd.)

Bosnia and Herzegovina (B&H) is among the European countries with the highest rate of air pollution-related death cases and the poorest air quality. The main causes are solid fuel consumption, traffic, and the poorly developed or implemented air pollution reduction policies. In addition, the city of Sarajevo, the capital of B&H, suffers temperature inversion episodes in autumn/winter months, which sustain air pollution. Human biomonitoring studies may be confounded by the lifestyle of subjects or possible metabolic alterations. Therefore, this study aimed to evaluate Ligustrum vulgare L. as a model for air pollution monitoring by measuring DNA damage at one rural and two urban sites. DNA damage was measured as tail intensity (TI) in L. vulgare leaves, considering seasonal, sampling period, leaf position and staging, and spatial (urban versus rural) variation. Effects of COVID-19 lockdown on TI were assessed by periodical monitoring at one of the selected sites, while in-house grown L. vulgare plants were used to test differences between outdoor and indoor air pollution effects for the same sampling period. Significantly higher TI was generally observed in leaves collected in Campus in December 2020 and 2021 compared with March (P < 0.0001). Outer and adult leaves showed higher TI values, except for the rural site where no differences for these categories were found. Leaves collected in the proximity of the intensive traffic showed significantly higher TI values (P < 0.001), regardless of the sampling period and the stage of growth. In regards to the COVID-19 lockdown, higher TI (P < 0.001) was registered in December 2020, after the lockdown period, than in periods before COVID-19 outbreak or immediately after the lockdown in 2020. This also reflects mild air pollution conditions in summer. TI values for the in-house grown leaves were significantly lower compared to those in situ. Results showed that L. vulgare may present a consistent model for the air pollution biomonitoring but further studies are needed to establish the best association between L. vulgare physiology, air quality data, and air pollution effects., (© The Author(s) 2022. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Air pollution, recognized as a human carcinogen, is a significant cause of death in industrial and developing countries, and Bosnia and Herzegovina (B&H) is one of the leading countries for air pollution-caused death rate and has the poorest urban air quality in Europe. Despite a population decrease, urban air pollution in B&H has increased due to traffic pollution and still intensive use of solid fuel for heating and cooking. Human biomonitoring studies, regarding the described air pollution, have not been conducted before, and particularly have not been conducted in the region of Sarajevo. Good health, well-being, and environmental protection are part of the 17 defined Sustainable Development Global Goals. Accordingly, this study aimed to determine baseline levels of DNA damage in a group of Sarajevo citizens and to compare seasonal variations in DNA damage in relation to the reported levels of air pollution. From 33 individuals included in the study, samples were collected in the summer and winter seasons. The buccal micronucleus cytome (BMCyt) assay and comet assay in leucocytes isolated from saliva were performed. Mean values and standard deviations of log-transformed tail intensity (%), tail length (µm), and tail moment results in winter were 1.14 ± 0.23, 2.20 ± 0.14, and 1.03 ± 0.29, respectively, while in the summer season those values were 1.19 ± 0.19, 2.25 ± 0.17, and 1.07 ± 0.25, respectively. No significant differences were found for the comet assay parameters. Nevertheless, BMCyt results showed significant increases in micronuclei (P = .008), binuclear cells (P = .04), karyolysis (P = .0003), condensed chromatin (P = .03), and pyknosis (P = .002) in winter. Although the results of comet and BMCyt assays are not in accordance, this study contributes to the human air pollution biomonitoring in Sarajevo, B&H, and based on the genotoxic effects of air pollution evidenced by the BMCyt biomarker further studies of this kind are necessary., (© The Author(s) 2022. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Apoptosis induction is a promising approach in targeting tumor cells. As halogenated boroxine (HB) shows antitumor activity, but its mechanism of action in hematological tumors remains unclear, in this study, we aimed to analyze apoptosis triggering in normal and UT-7 leukemia cells by HB. Methods for assessing cell viability and cytotoxicity, apoptosis detection, relative expression of 84 apoptosis-associated genes and BCL-2, and functional analysis were applied. Pronounced HB activities in inhibition of cell viability, cytotoxicity, and apoptosis induction with measurable differences between tumor and normal cells were found. HB modulated the expression of 21 genes, predominantly downregulated the antiapoptotic genes in leukemia. The functional association revealed HB's impact on inhibition of NF-κB signaling pathway. BCL-2 expression decreasing was found only in UT-7 leukemia. This study identified HB as an apoptosis inducer affecting leukemia but not normal cells considering mechanisms of selective activity that may be a great advantage of HB applications., (© 2022 Wiley Periodicals LLC.)

Recently it was found that dipotassium-trioxohydroxytetrafluorotriborate, K2(B3O3F4OH), is a potent and highly specific inhibitor of precancerous cell processes. We conducted gene expression profiling of human melanoma cells before and after treatment with two concentrations (0.1 and 1 mM) of this boron inorganic derivative in order to assess its effects on deregulation of genes associated with tumor pathways. Parallel trypan blue exclusion assay was performed to assess the cytotoxicity effects of this chemical. Treatment with K2(B3O3F4OH) induced a significant decrease of cell viability in melanoma cellline at both tested concentrations. Furthermore, these treatments caused deregulation of more than 30 genes known as common anti-tumor drug targets. IGF-1 and hTERT were found to be significantly downregulated and this result may imply potential use of K2(B3O3F4OH) as an inhibitor or human telomerase and insulin-like growth factor 1, both of which are associated with various tumor pathways.

We have examined antiproliferative, cytotoxic, and genotoxic potential of a halogenated boroxine dipotassium trioxohydroxytetrafluorotriborate (K₂[B₃O₃F₄OH]). The impact on cell growth was evaluated by alamarBlue assay in basal cell carcinoma culture. Cytostatic, cytotoxic, and genotoxic potential were evaluated in lymphocytes culture, applying cytokinesis-block micronucleus cytome assay and chromosome aberrations analysis. Tested concentrations (0.05, 0.1, 0.2, and 0.4 mg/mL) were correlated with inhibition of cell growth in basal cell carcinoma culture and with the lymphocytes proliferation. Clastogenic activity has been confirmed, without evidences of aneugenic activity, in human lymphocytes.

Cytogenetic biomarkers, such as micronuclei in peripheral blood or oral mucosa, are widely used for evaluation of exposure to genotoxins or carcinogens. Tobacco is one of the strongest carcinogens, responsible for development of different types of cancers. The aim of this study was to assess the genotoxicity of cigarette consumption in young smokers and to correlate results of cytogenetic analysis in peripheral blood lymphocytes and exfoliated buccal cells. The study was conducted on samples taken from 43 smokers and 44 non-smokers, young individuals from Bosnia and Herzegovina. Significantly higher frequency of micronuclei in peripheral blood lymphocytes was observed in smokers (p < 0.05). No significant correlations were found for age, duration and intensity of smoking, and frequency of micronuclei in lymphocytes. Significantly higher frequency of degenerated (apoptotic) buccal cells was also revealed in smokers (p < 0.05). The frequency of apoptotic cells in smokers was significantly influenced by the age of participants (F = 8.649; p < 0.01) and duration of smoking (F = 5.389; p < 0.05). Results of cytogenetic analysis conducted in peripheral blood and exfoliated buccal cells are in significant positive correlation, indicating complementarities of those analyses.

Paracetamol is a common analgesic and antipyretic drug. It has been recognized as one of the most ordinary medications taken in overdoses. We examined the possible genotoxic effects of high paracetamol concentrations expected to occur after overdose. Paracetamol was added to the cultures at the beginning of the cultivation period. Separate cultures for three tested concentrations of paracetamol (50 microg/mL, 100 microg/mL, and 200 microg/mL) were set. Effects of paracetamol were evaluated by micronucleus cytokinesis-block assay, chromosome aberration analysis, and nuclear division index. Results demonstrate that paracetamol concentration of 200 microg/mL expresses certain genotoxic effects in human peripheral blood lymphocytes.

Observation of micronuclei presents reliable method for evaluation of genotoxicity effects on chromosomal level. One of genotoxins evidenced in the environment as impact of the last conflict in Bosnia and Herzegovina is depleted uranium. This research included an evaluation of genctic load in lymphocytes of individuals from population exposed to depleted uranium and the control group in correlation with sex, age and smoking habit. Results have shown increased micronuclei formation within exposed population and their statistically significant correlation with ages.