Genotoxic effects of inorganic molecule dipotassium-trioxohydroxytetrafluorotriborate, K2(B3O3F4OH), a promising new therapeutic for the epidermal changes treatment, have been evaluated. In vitro analysis included evaluation of genotoxic and cytotoxic potential of K2(B3O3F4OH) in concentrations of 0.01, 0.02, 0.05 and 0.06 mg/mL applying cytokinesis-block micronucleus cytome assay in human lymphocyte culture. With the increase of concentration the frequency of micronuclei elevated but the differences were not significant. Also, there were no significant differences among the frequencies of nuclear buds and nucleoplasmic bridges between controls and treated cultures. Nuclear division index and nuclear division cytotoxycity index values did not reveal significant cytotoxic effect of K2(B3O3F4OH). In vivo genotoxic effects were analyzed on BALB/c mice applying reticulocytes micronucleus assay. K2(B3O3F4OH) was administrated intraperitoneally in final concentrations of 10, 20, 50 and 55 mg/kg. Significant decrease of reticulocytes ratio and increase of micronuclei frequencies against pre-treatments were found for both sampling periods of 48 and 72 hours of the highest applied concentration. This study confirmed that K2(B3O3F4OH) is not genotoxic in tested concentrations in vitro as well as in concentrations lower than 55 mg/kg in vivo. This study presents a reliable basis for further pre-clinical and potential clinical investigations.

Introduction: Bioflavonoids delphinidin (2-(3,4,5-Trihydroxyphenyl)chromenylium-3,5,7-triol) and luteolin (2-(3,4-Dihydroxyphenyl)-5,7-dihydroxy-4-chromenone) have been recognized as promising antioxidants and anticancer substances. Due to their extensive use, the goal of the research was to determine whether they have any genotoxic potential in vitro.Methods: Analysis of genotoxic potential was performed applying chromosome aberrations test in human lymphocyte culture, as this kind of research was not conducted abundantly for these two bioflavonoids. Delphinidin and luteolin were dissolved in DMSO and added to cultures in final concentrations of 25, 50 and 100 μM.Results: In human lymphocytes cultures Delphinidin induced PCDs in all treatments, potentially affecting the cell cycle and topoisomerase II activity. In concentration of 50 μM luteolin showed strong genotoxic effects and caused significant reduction of cell proliferation.Conclusion: Luteolin exhibited certain genotoxic and cytostatic potential. Delphinidin was not considered genotoxic, however its impact on mitosis, especially topoisomerase II activity, was revealed.

Abstract The genotoxicity of halogenated boroxine [K2(B3O3F4OH)], a novel compound with the potential for prevention and/or treatment of various skin changes, has been confirmed in human lymphocytes. The potential of luteolin and delphinidin in inhibition of the genotoxic and cytotoxic effects of halogenated boroxine in vitro was analyzed applying the chromosome aberration analysis and the cytokinesis-block micronucleus cytome assay in human lymphocyte cultures. The in vitro treatments included addition of boroxine and flavonoids independently, and combined treatments of boroxine with luteolin or delphinidin. In the concentration of 50 μM, luteolin significantly decreased the frequency of micronuclei and nuclear buds. Delphinidin suppressed the occurrence of aberrant cells in the presence of the halogenated boroxine, but also affected their induction in respective delphinidin treatment. Detection of endoreduplications in combined treatments indicated that these flavonoids are potential inhibitors of cell cycle or topoisomerase II activity. The obtained results have confirmed antigenotoxic activity of selected bioflavonoids in vitro. The side effects of potential therapeutic applications of halogenated boroxine may be inhibited in the presence of bioflavonoids in appropriate dosage.

Lilium martagon L. var. cattaniae Vis. (Liliaceae) is endemic plant of Dinaridi mountain. In this work we established protocol for fast in vitro propagation and multiplication of Lilium martagon var. cattaniae. The aim was to enable fast production of plant material as potential source of pharmaceutically valuable secondary metabolites. Seeds of L.martagon var. cattaniae were germinated on a Murashige and Skoog basal medium with a supplement of 0.15 mg/l gibberellic acid (GA3), and multiplication was performed on MS medium supplemented with 0.1 mg/l gibberellic acid (GA3), 0.2 mg/l indole-3-butyric acid (IBA) and 0.5 mg/l 6-ben- zylaminopurine (BAP). We used ultrasound assisted extraction to prepare extracts of leaves and bulbs of Lilium martagon var. cattaniae, which were evaluated for their genotoxic potential using Allium test and cytokinesis-block micronucleus test in human lymphocytes culture. There was statistically significant difference between all used concentrations of lilium extracts and control on proliferation of cells of root tip of onion (Allium cepa). In cytokinesis-block micronucleus test no statistically significant difference between frequencies of analyzed parameters in samples treated with tested concentrations of extracts and control was obtained.

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.