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Epigenotoxicology needs simple and fast tools to assess xenobiotic epigenetic load. This work proposes a comet assay modification designed to detect global methylation changes (Methy-sens Comet) through enzymatic digestion with two restriction enzymes (HpaII, MspI). In the methylation-sensitive protocol tested for repeatability on A549 cells, nickel chloride induced hypermethylation and decitabine-induced hypomethylation. A concomitant assessment of DNA methyltransferases (DNMTs) genes transcriptional levels has been performed, to implement a multifunctional approach to epigenotoxicology. Methy-sens Comet showed a general good repeatability and sensitivity to methylation changes while DNMTs transcriptional levels granted additional proof of xenobiotic-induced impairment of methylome maintenance. [ABSTRACT FROM AUTHOR]

BACKGROUND: In the human diet, the consumption of fresh fruits and vegetables is important inmaintaining good health and in preventing chronic diseases. It is known that plant-derived food is a powerful source of chemopreventive molecules, i.e. antioxidants, and spinach (Spinacia oleracea L., Chenopodiaceae) possesses a wide range of metabolites with such biological activity. Plant stress response could lead to the production of metabolites with high value for human health and this could be a tool to enhance the production of molecules with antioxidant activity in plants. RESULTS: Data reported in this paper confirm the antioxidant properties of spinach plants, and show a strong antiproliferative activity of leaf extract on HT-29 human cell line. Besides, the hypoxic stress seems to affect the pool of antioxidant molecules present in spinach leaves, as verified bymeans of HPLC-MS/MS analysis and the aluminium chloride and ABTS assays. CONCLUSION: Our findings represent a basis for improving the biological and pharmacological properties of spinach plants, including the use of different growth conditions tomodulate the phytocomplex profile of spinach. [ABSTRACT FROM AUTHOR]

Epidemiological evidence shows that regular consumption of Brassicaceae is associated with a reduced risk of cancer and heart disease. Cruciferous species are usually processed before eating and the real impact of cooking practices on their bioactive properties is not fully understood. We have evaluated the effect of common cooking practices (boiling, microwaving, and steaming) on the biological activities of broccoli, cauliflower and Brussels sprouts. Anti-proliferative and chemoprotective effects towards DNA oxidative damage of fresh and cooked vegetable extracts were evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium and Comet assays on HT-29 human colon carcinoma cells. The fresh vegetable extracts showed the highest anti-proliferative and antioxidant activities on HT-29 cells (broccoli>cauliflower = Brussels sprouts). No genotoxic activity was detected in any of the samples tested. The cooking methods that were applied influenced the anti-proliferative activity of Brassica extracts but did not alter considerably the antioxidant activity presented by the raw vegetables. Raw, microwaved, boiled (except broccoli) and steamed vegetable extracts, at different concentrations, presented a protective antioxidative action comparable with vitamin C (1 mm). These data provide new insight into the influence of domestic treatment on the quality of food, which could support the recent epidemiological studies suggesting that consumption of cruciferous vegetables, mainly cooked, may be related to a reduced risk of developing cancer. [ABSTRACT FROM AUTHOR]

Air pollutants, especially PM, have been found to determine various effects on human health, including genotoxic effects. The aim of this study was to assess DNA damage with micronuclei (MN) and comet tests on buccal cells of 6–8 years old children living in an area with high air pollution. Both tests were repeated in the same children in two consecutive winters to compare the levels of DNA damage under different pollution conditions. A complete data set including lifestyle, air pollutants levels and biological sampling was available for 180 children in the two winters. A high mean MN frequency was found in both seasons, with higher value in the first (0.51 ± 0.59) than the second winter (0.40 ± 0.52), whereas DNA damage measured with comet test showed higher damage in the second versus the first winter (visual score 208.8 ± 67.1 vs. 173.2 ± 50.8). The associations between air pollutant levels (CO, NO2, SO2, benzene, O3, PM10, and PM2.5; PM0.5 and PAHs) and DNA damage were investigated at different lag times, and mainly, no significant association was found. This study on repeated measure of MN frequency and DNA damage in children's buccal did not show an association with various air pollutants evaluated in an area with high levels of air pollution. [ABSTRACT FROM AUTHOR]

Urban airborne particulate is a complex mixture of air pollutants, many of which have not been identified. However, short-term mutagenesis tests together with chemicophysical parameter analysis are able to better assess air quality and genotoxic load. The findings of continuous monitoring (January 1991–August 1998) of urban air genotoxicity of a Po Valley town (Italy) on Salmonella typhimurium and Saccharomyces cerevisiae are reported. During this period, various measures (catalytic devices, unleaded fuels, annual vehicle overhaul, etc.) to improve air-dispersed pollutant control were enforced. However, a continuous presence of genotoxic compounds is shown and more qualitative than quantitative changes are evident. We also demonstrate the ability of the Comet assay to detect DNA-damaging agents in airborne particulate samples. We applied the test to human leukocytes and, with major improvements, to plant cells (Allium cepa roots and epigean tissues of Impatiens balsamina). The first findings on human leukocytes confirm the sensitivity of this assay, its peculiarity and its applicability in assessing genotoxicity in environmental samples. The capability of plants to show the response of multicellular organisms to environmental pollutants largely counterbalances a probable lowering in sensitivity. Moreover, application of the Comet test to epigean tissues could be useful in estimating the bioavailability of and genotoxic damage by air pollutants, including volatile compounds (ozone, benzene, nitrogen oxides, etc.) to higher plants. [ABSTRACT FROM PUBLISHER]

The genotoxic effects of the antiblastic drug bleomycin were studied in the D7 strain of Saccharomyces cerevisiae and on its derivative mitochondrial mutant ρ° at different cellular concentrations of two drug metabolizing systems, glutathione (GSH) and cytochrome P-450. Bleomycin mutagenic activity was evaluated as frequencies of mitotic gene conversion, reversion and total aberrations under different physiological conditions. In the D7 strain, petite mutant induction was also detected. This is important due to the role of the mitochondrial genome in cancer induction, ageing and degenerative diseases. Both strains showed higher convertant than revertant induction. At high cytochrome P-450 levels, bleomycin-induced gene conversion was enhanced in both strains although mitochondrial functionality showed a detoxicant role while cellular GSH content decreased the induction of convertants only in the respiratory proficient strain. Cell metabolic conditions, such as cell cycle, aerobic/hypoxic conditions of the cell and content of drug metabolizing enzymes, appeared to interact with the genotoxic effectiveness of bleomycin. Moreover, the usefulness of S.cerevisiae as a model organism for drug assessment for mutagenicity was emphasized. [ABSTRACT FROM PUBLISHER]

The control of the fungal contamination on crops is considered a priority by the sanitary authorities of an increasing number of countries, and this is also due to the fact that the geographic areas interested in mycotoxin outbreaks are widening. Among the different pre- and post-harvest strategies that may be applied to prevent fungal and/or aflatoxin contamination, fungicides still play a prominent role; however, despite of countless efforts, to date the problem of food and feed contamination remains unsolved, since the essential factors that affect aflatoxins production are various and hardly to handle as a whole. In this scenario, the exploitation of bioactive natural sources to obtain new agents presenting novel mechanisms of action may represent a successful strategy to minimize, at the same time, aflatoxin contamination and the use of toxic pesticides. The Aflatox® Project was aimed at the development of new-generation inhibitors of aflatoxigenic Aspergillus spp. proliferation and toxin production, through the modification of naturally occurring molecules: a panel of 177 compounds, belonging to the thiosemicarbazones class, have been synthesized and screened for their antifungal and anti-aflatoxigenic potential. The most effective compounds, selected as the best candidates as aflatoxin containment agents, were also evaluated in terms of cytotoxicity, genotoxicity and epi-genotoxicity to exclude potential harmful effect on the human health, the plants on which fungi grow and the whole ecosystem. [ABSTRACT FROM AUTHOR]

Abstract: This paper reports the syntheses and characterization of ethylmorpholine substituted citronellal thiosemicarbazone copper(II) and nickel(II) metal complexes. The compounds were characterized through elemental analyses and spectroscopic (IR, UV–Vis, NMR, MS) methods. The X-ray analysis of the two complexes shows that both Ni and Cu derivatives present a square planar coordination, where the coordinating homologous donor atoms bind in trans to each other. The compounds were tested for their biological activity after determination of their octanol–saline partition coefficients, followed by their radical scavenging properties. Eventually the complexes were tested for their proliferation inhibition on human histiocytic lymphoma U937 cell line. The GI50 values resulted to be 2.3μM for the copper derivative and 12.3μM for the nickel derivative. [Copyright &y& Elsevier]

The impact of emerging chemical pollutants, on both status and functionality of aquatic ecosystems is worldwide recognized as a relevant issue of concern that should be assessed and managed by researchers, policymakers, and all relevant stakeholders. In Europe, the Reach Regulation has registered more than 100.000 chemical substances daily released in the environment. Furthermore, the effects related to the mixture of substances present in aquatic ecosystems may not be predictable on the basis of chemical analyses alone. This evidence, coupled with the dramatic effects of climate changes on water resources through water scarcity and flooding, makes urgent the application of innovative, fast and reliable monitoring methods. In this context, Effect-Based Methods (EBMs) have been applied in the urban stretch of the Tiber River (Central Italy) with the aim of understanding if detrimental pressures affect aquatic environmental health. In particular, different eco-genotoxicological assays have been used in order to detect genotoxic activity of chemicals present in the river, concurrently characterized by chemical analysis. Teratogenicity and embryo-toxicity have been studied in order to cover additional endpoints. The EBMs have highlighted the presence of diffuse chemical pollution and ecotoxicological effects in the three sampling stations, genotoxicological effects have been also detected through the use of different tests and organisms. The chemical analyses confirmed that in the aquatic ecosystems there is a diffuse presence, even at low concentrations, of emerging contaminants such as pharmaceuticals, not routinely monitored pesticides, personal care products, PFAS. The results of this study can help to identify an appropriate battery of EBMs for future studies and the application of more appropriate measures in order to monitor, mitigate or eliminate chemical contamination and remediate its adverse/detrimental effects on the ecosystem health. [Display omitted] • Evaluation of Tiber River water quality combining Effect Based Methods and chemical analysis. • In vivo and i n vitro eco-genotoxicity assays to study the potential effects of Tiber River water. • Recommendations to include a battery of Effect-Based Methods in preventive management measures. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is the leading cause of death in industrialized countries and affects an increasing number of people. Several risk factors play an important role in the etiology of this disease, such as an unhealthy lifestyle. It is increasingly clear that genetic factors influencing the molecular basis of excitation-contraction mechanisms in the heart could contribute to modify the individual's risk. Thanks to the progress that has been made in understanding calcium signaling in the heart, it is assumed that calmodulin can play a crucial role in the excitation-contraction coupling. In fact, calmodulin (CaM) binds calcium and consequently regulates calcium channels. Several works show how some polymorphic variants can be considered predisposing factors to complex pathologies. Therefore, we hypothesize that the identification of polymorphic variants of proteins involved in the CaM pathway could be important for understanding how genetic traits can influence predisposition to myocardial infarction. This review considers each pathway of the three different isoforms of calmodulin (CaM1; CaM2; CaM3) and focuses on some common proteins involved in the three pathways, with the aim of analyzing the polymorphisms studied in the literature and understanding if they are associated with cardiovascular disease. [ABSTRACT FROM AUTHOR]

Thiosemicarbazones (TSC) and their metal complexes display diverse biological activities and are active against multiple pathological conditions ranging from microbial infections to abnormal cell proliferation. Ribonucleotide reductase (RNR) is considered one of the main targets of TSCs, yet, the existence of additional targets, differently responsible for the multifaceted activities of TSCs and their metal complexes has been proposed. To set the basis for a more comprehensive delineation of their mode of action, we chemogenomically profiled the cellular effects of bis(citronellalthiosemicarbazonato)nickel(II) [Ni(S-tcitr)2] using the unicellular eukaryote Saccharomyces cerevisiae as a model organism. Two complementary genomic phenotyping screens led to the identification of 269 sensitive and 56 tolerant deletion mutant strains and of 14 genes that when overexpressed make yeast cells resistant to an otherwise lethal concentration of Ni(S-tcitr)2. Chromatin remodeling, cytoskeleton organization, mitochondrial function and iron metabolism were identified as lead cellular processes responsible for Ni(S-tcitr)2 toxicity. The latter process, and particularly glutaredoxin-mediated iron loading of RNR, was found to be affected by Ni(S-tcitr)2. Given the multiple pathways regulated by glutaredoxins, targeting of these proteins by Ni(S-tcitr)2 can negatively affect various core cellular processes that may critically contribute to Ni(S-tcitr)2 cytotoxicity. [ABSTRACT FROM AUTHOR]

Abstract Methionine deprivation of cancer cells, which are deficient in methionine biosynthesis, has been envisioned as a therapeutic strategy to reduce cancer cell viability. Methionine γ-lyase (MGL), an enzyme that degrades methionine, has been exploited to selectively remove the amino acid from cancer cell environment. In order to increase MGL catalytic activity, we performed sequence and structure conservation analysis of MGLs from various microorganisms. Whereas most of the residues in the active site and at the dimer interface were found to be conserved, residues located in the C-terminal flexible loop, forming a wall of the active site entry channel, were found to be variable. Therefore, we carried out site-saturation mutagenesis at four independent positions of the C-terminal flexible loop, P357, V358, P360 and A366 of MGL from Citrobacter freundii , generating libraries that were screened for activity. Among the active variants, V358Y exhibits a 1.9-fold increase in the catalytic rate and a 3-fold increase in K M , resulting in a catalytic efficiency similar to wild type MGL. V358Y cytotoxic activity was assessed towards a panel of cancer and nonmalignant cell lines and found to exhibit IC 50 lower than the wild type. The comparison of the 3D-structure of V358Y MGL with other MGL available structures indicates that the C-terminal loop is either in an open or closed conformation that does not depend on the amino acid at position 358. Nevertheless, mutations at this position allosterically affects catalysis. Highlights • The C-terminal loop of C. freundii MGL is highly variant. • Most mutations at positions P357, V358, P360 and A366 cause enzyme inactivation. • Variant V358Y showed two-fold increase in catalytic rate and K M. • Comparison of X-ray structures of MGLs and V358Y suggests a conformational adaptation to mutations. [ABSTRACT FROM AUTHOR]

In this paper, citronellal, vanillin and pyridoxal thiosemicarbazones were modified with polar substituents, namely ethylmorpholine and glucose, to increase their polarity and compare the effects of these moieties on their biological activity. Altogether, nine ligands were synthesized and for each of them also their copper(II) and nickel(II) complexes were prepared and used for the biological tests. Eventually, assays on proliferation inhibition were conducted using leukemic cell line U937, already used as a model for previous citronellal thiosemicarbazone tests. Biological tests were also performed on solid tumor cell line HT29. From the first screenings, two of the metal complexes showed remarkable interesting properties, and, therefore, were also tested for histosensitivity. [ABSTRACT FROM AUTHOR]

The mycotoxin zearalenone may contaminate food and feed worldwide upon infections by Fusarium spp. of plants and raw materials intended for human and animal consumption. Currently, contamination by zearalenone and congeners pose concern for health due to xenoestrogenic effects. However, while zearalenone and the main reduced metabolites are well-known xenoestrogens, some plant metabolites that may enter the food chain have been observed aside. Among them, zearalenone-14-glucoside may be abundant in the edible parts of infected plants, thereby entering significantly the human diet and animal feeding. On the basis of previous works, the lack of xenoestrogenicity for this compound per se was taken for granted, while neglecting the direct proof of estrogenic activity and considering the hydrolysis as a possible source of estrogenically active metabolites. The present work investigated the xenoestrogenicity of zearalenone-14-glucoside, in comparison to zearalenone, deepening the underlying molecular mechanisms through an integrated in vitro/in silico approach. On the basis of our results, zearalenone-14-glucoside effectively stimulated a xenoestrogenic response in cells, but such stimulus can be entirely attributable to the hydrolysis phenomenon, as the glycosylated form turned out to be unable to effectively bind and activate the estrogens receptors. [ABSTRACT FROM AUTHOR]

Aflatoxins represent a serious problem for a food economy based on cereal cultivations used to fodder animal and for human nutrition. The aims of our work are two-fold: first, to perform an evaluation of the activity of newly synthesized thiosemicarbazone compounds as antifungal and anti-mycotoxin agents and, second, to conduct studies on the toxic and genotoxic hazard potentials with a battery of tests with different endpoints. In this paper we report an initial study on two molecules: S-4-isopropenylcyclohexen-1-carbaldehydethiosemicarbazone and its metal complex, bis(S-4-isopropenylcyclohexen-1-carbaldehydethiosemicarbazonato)nickel (II). The outcome of the assays on fungi growth and aflatoxin production inhibition show that both molecules possess good antifungal activities, without inducing mutagenic effects on bacteria. From the assays to ascertain that the compounds have no adverse effects on human cells, we have found that they are cytotoxic and, in the case of the nickel compound, they also present genotoxic effects. [ABSTRACT FROM AUTHOR]

There are no reports of saccharolytic enzymes being used in the preparation of formulations for animal semen extenders. In the present study, the use of an innovative semen extender (Formula12 ® ) in the long-term liquid storage of boar semen at 17 °C was evaluated. The formulation included use of a disaccharide (sucrose) as the energy source precursor coupled to an enzymatic agent (invertase). The innovative extender was evaluated and compared in vitro to a commercial extender (Vitasem LD ® ) for the following variables: Total Motility (TM), Forward Progressive Motility (FPM), sperm morphology, membrane integrity, acrosome integrity, and chromatin instability. Boar sperm diluted in Formula12 ® and stored for 12 days at 17 °C maintained a commercially acceptable FPM (>70%). Using the results from the in vitro study, an AI field trial was performed. A total of 170 females were inseminated (135 with Formula12 ® and 35 with Vitasem LD ® ). The pregnancy rates were 97.8% compared with 91.4%, and the farrowing rates were 96.3% compared with 88.6% when Formula12 ® and Vitasem LD ® were used, respectively. The mean number of piglets born/sow were 14.92 ± 0.46 compared with 13.83 ± 0.70, and the number of piglets born alive/sow were 14.07 ± 0.46 compared with 12.12 ± 0.70 ( P < 0.05). The results obtained in this study demonstrated that use of the innovative concept to provide a precursor of glucose and fructose as energy sources for an enzymatic agent in an extender allowed for meeting the metabolic requirements of boar sperm during storage at 17 °C. It is suggested that there was a beneficial effect on fertilizing capacity of boar sperm in the female reproductive tract with use of these technologies. [ABSTRACT FROM AUTHOR]

ARPA Emilia Romagna created, in 1997, a regional network for the continuous monitoring of the mutagenicity of PM2.5 by short-term mutagenicity bioassays to guarantee a constant surveillance on the entire regional territory. The continuous monitoring of the PM mutagenicity provides essential information for a better understanding of the impact of air pollution on the health of the population, and allows one to better judge the efficiency of national and local efforts for urban air quality improvement (use of ‘green’ petrol and ecodiesel, days during which traffic is prohibited, etc.). This article presents the results relating to the Network''s activity between September 2000 and December 2002, on PM2.5 fraction. The organic extracts of PM2.5 were tested for mutagenicity using Salmonella tester strains TA98 and TA100 with and without metabolic activation (S9). The data obtained on the genotoxicity of air particulate extracts have revealed a constant presence of mutagenic substances adsorbed on particulate matter—with a prevalence of direct-acting mutagens than of promutagens—in a typical seasonal trend featuring higher levels in autumn–winter and lower in warmer periods of the year. In this work the evolution of PM2.5 mutagenicity was compared with the particles, carbon monoxide (CO) and nitrogen dioxide (NO2) concentrations (monthly average); these comparisons revealed a quite good level of agreement on a local basis. [Copyright &y& Elsevier]

The impact of gender and diet on the proteome of Longissimus dorsi was addressed by 2D-PAGE analysis of male and female pigs, fed with a barley-based control diet and a diet enriched with extruded linseed and plant extracts. No statistically significant difference in protein number between female and male samples was found. Furthermore, PCA excluded gender-dependent protein clusters. For both the control and enriched diet, several spots exhibited at least a 1.5-fold intensity difference, but none showed a statistically relevant variation. Protein profiles PCA for both diets indicated that the first two principal components account up to 47% of total variance, with two diet-dependent separated clusters. Among 176 common spots, 29 exhibited >1.5 fold change, mostly more abundant in the control diet. PMF identified 14 distinct proteins, including myofibrillar proteins, glycolytic enzymes and myoglobin, thus suggesting a diet-dependent meat quality. A statistically significant increase in carbonylated proteins of enriched diet samples was detected using the 2,4-dinitrophenylhydrazine method but not using fluorescein-5-thiosemicarbazide-labeled bands. ROS induction and DNA oxidative damage, detected in a human cell line exposed to digested meat from both diets, further support the notion that the enriched diet does not protect against oxidative stress. The comparison of the protein profile of female and male Longissimus dorsi from pigs fed by a control diet and a diet enriched with polyphenols, indicate no gender effect, whereas diet affects the abundance of several proteins, possibly linked to meat quality. Protein carbonylation was statistically higher in meat from the enriched diet, suggesting that polyphenols at the concentration present in the diet did not exert a protective effect against oxidation. Unlabelled Image [ABSTRACT FROM AUTHOR]

Research in the field of metallodrugs is continually increasing. However, it is often limited by the poor solubility in water of the metal complexes. To try to overcome this problem, the two new ligands bis-(sodium 3-methoxy-5-sulfonate-salicylaldehyde)thiocarbohydrazone ( bis-TCH , Na 2 H 4 L 1 ) and bis-(sodium 3-methoxy-5-sulfonate-salicylaldehyde)carbohydrazone ( bis-CH , Na 2 H 4 L 2 ) were synthesized and characterized, both achieving high solubility in water. The speciation of the ligands and their coordinating behaviour towards the biologically relevant Cu(II) and Zn(II) ions were studied spectroscopically and potentiometrically, determining the p K a s of the ligands and the formation constants of the complex species. The monometallic and bimetallic Cu(II) and Zn(II) complexes were isolated, and the single-crystal X-ray structure of [Cu 2 (NaHL 1 )(H 2 O) 7 ] . 3.5H 2 O was discussed. Finally, preliminary studies of the in vitro cytotoxic properties of the new compounds were started on normal (Hs27) and cancer (U937) cell lines. bis-TCH was able to induce a growth inhibition effect between 40% and 45% in both cell lines; bis-CH did not produce a reduction in cell viability in Hs27 cells but revealed mild antiproliferative activity after 72 h of treatment in U937 cancer cells (GI 50 = 46.5 ± 4.94 μg/mL). Coordination of the Cu(II) ions increased the toxicity of the compounds, while, in contrast, Zn(II) complexes were not cytotoxic.

This review article explores the innovative field of eco-friendly cyclodextrin-based coordination polymers and metal-organic frameworks (MOFs) for transdermal drug delivery in the case of skin cancer therapy. We critically examine the significant advancements in developing these nanocarriers, with a focus on their unique properties such as biocompatibility, targeted drug release, and enhanced skin permeability. These attributes are instrumental in addressing the limitations inherent in traditional skin cancer treatments and represent a paradigm shift towards more effective and patient-friendly therapeutic approaches. Furthermore, we discuss the challenges faced in optimizing the synthesis process for large-scale production while ensuring environmental sustainability. The review also emphasizes the immense potential for clinical applications of these nanocarriers in skin cancer therapy, highlighting their role in facilitating targeted, controlled drug release which minimizes systemic side effects. Future clinical applications could see these nanocarriers being customized to individual patient profiles, potentially revolutionizing personalized medicine in oncology. With further research and clinical trials, these nanocarriers hold the promise of transforming the landscape of skin cancer treatment. With this study, we aim to provide a comprehensive overview of the current state of research in this field and outline future directions for advancing the development and clinical application of these innovative nanocarriers.

Since the discovery of cisplatin, the search for metal-based compounds with therapeutic potential has been a challenge for the scientific community. In this landscape, thiosemicarbazones and their metal derivatives represent a good starting point for the development of anticancer agents with high selectivity and low toxicity. Here, we focused on the action mechanism of three metal thiosemicarbazones [Ni(tcitr) 2 ], [Pt(tcitr) 2 ], and [Cu(tcitr) 2 ], derived from citronellal. The complexes were already synthesized, characterized, and screened for their antiproliferative activity against different cancer cells and for genotoxic/mutagenic potential. In this work, we deepened the understanding of their molecular action mechanism using an in vitro model of a leukemia cell line (U937) and an approach of transcriptional expression profile analysis. U937 cells showed a significant sensitivity to the tested molecules. To better understand DNA damage induced by our complexes, the modulation of a panel of genes involved in the DNA damage response pathway was evaluated. We analyzed whether our compounds affected cell cycle progression to determine a possible correlation between proliferation inhibition and cell cycle arrest. Our results demonstrate that metal complexes target different cellular processes and could be promising candidates in the design of antiproliferative thiosemicarbazones, although their overall molecular mechanism is still to be understood.

In this study, we assess the DNA damage occurring in response to cadmium (Cd) in the Cd hyperaccumulator Noccaea caerulescens Ganges (GA) vs the non-accumulator and close-relative species Arabidopsis thaliana. At this purpose, the alkaline comet assay was utilized to evaluate the Cd-induced variations in nucleoids and the methy-sens comet assay, and semiquantitative real-time (qRT)-PCR were also performed to associate nucleus variations to possible DNA modifications. Cadmium induced high DNA damages in nuclei of A. thaliana while only a small increase in DNA migration was observed in N. caerulescens GA. In addition, in N. caerulescens GA, CpG DNA methylation increase upon Cd when compared to control condition, along with an increase in the expression of MET1 gene, coding for the DNA-methyltransferase. N. caerulescens GA does not show any oxidative stress under Cd treatment, while A. thaliana Cd-treated plants showed an upregulation of transcripts of the respiratory burst oxidase, accumulation of reactive oxygen species, and enhanced superoxide dismutase activity. These data suggest that epigenetic modifications occur in the N. caerulescens GA exposed to Cd to preserve genome integrity, contributing to Cd tolerance., (© 2022. The Author(s).)

Background: Nanotoxicology is an increasingly relevant field and sound paradigms on how inhaled nanoparticles (NPs) interact with organs at the cellular level, causing harmful conditions, have yet to be established. This is particularly true in the case of the cardiovascular system, where experimental and clinical evidence shows morphological and functional damage associated with NP exposure. Giving the increasing interest on cobalt oxide (Co 3 O 4 ) NPs applications in industrial and bio-medical fields, a detailed knowledge of the involved toxicological effects is required, in view of assessing health risk for subjects/workers daily exposed to nanomaterials. Specifically, it is of interest to evaluate whether NPs enter cardiac cells and interact with cell function. We addressed this issue by investigating the effect of acute exposure to Co 3 O 4 -NPs on excitation-contraction coupling in freshly isolated rat ventricular myocytes., Results: Patch clamp analysis showed instability of resting membrane potential, decrease in membrane electrical capacitance, and dose-dependent decrease in action potential duration in cardiomyocytes acutely exposed to Co 3 O 4 -NPs. Motion detection and intracellular calcium fluorescence highlighted a parallel impairment of cell contractility in comparison with controls. Specifically, NP-treated cardiomyocytes exhibited a dose-dependent decrease in the fraction of shortening and in the maximal rate of shortening and re-lengthening, as well as a less efficient cytosolic calcium clearing and an increased tendency to develop spontaneous twitches. In addition, treatment with Co 3 O 4 -NPs strongly increased ROS accumulation and induced nuclear DNA damage in a dose dependent manner. Finally, transmission electron microscopy analysis demonstrated that acute exposure did lead to cellular internalization of NPs., Conclusions: Taken together, our observations indicate that Co 3 O 4 -NPs alter cardiomyocyte electromechanical efficiency and intracellular calcium handling, and induce ROS production resulting in oxidative stress that can be related to DNA damage and adverse effects on cardiomyocyte functionality.

The data included in this paper are associated with the research article entitled "Markers for toxicity to HepG2 exposed to cadmium sulphide quantum dots; damage to mitochondria" (Paesano et al.) [1]. The article concerns the cytotoxic and genotoxic effects of CdS QDs in HepG2 cells and the mechanisms involved. In this dataset, changes in expression levels of candidate genes are reported, together with details concerning synthesis and properties of CdS QDs, additional information obtained through literature survey, measures of the mitochondrial membrane potential and the glutathione redox state.

Objective: Evaluation of cytotoxic and genotoxic load of drinking water in relationship to the source of supplies, the disinfection process, and the piping system., Setting: Two treatment/distribution networks of drinking water, the first (#1) located near the source, the second (#2) located near the mouth of a river supplying the plants., Design: Water samples were collected before (F) and after (A) the disinfection process and in two points (R1 and R2) of the piping system. The samples, concentrated on C18, were tested for DNA damage in human leukocytes by the Comet assay and for gene conversion, reversion and mitochondrial mutability in Saccharomyces cerevisiae D7 strain., Main Outcome Measures: The approach used in this study is able to identify genotoxic compounds at low concentration and evaluate their antagonism/synergism in complex mixtures., Results: Comet assay results show that the raw water quality depends on the sampling point, suggesting that a high input of environmental pollutants occurred during river flowing; they also show that the disinfection process can both detoxify or enhance biological activity of raw water according to its quality and that the piping systems do not affect tap water cytotoxic/genotoxic load. The yeast tests indicate the presence of some disinfection by-products effective on mitochondrial DNA., Conclusion: The biological assays used in this study are proven to be able to detect the presence of low concentrations of toxic/genotoxic compounds and assess the sources of their origin/production.

ARPA Emilia Romagna created, in 1997, a regional network for the continuous monitoring of the mutagenicity of PM(2.5) by short-term mutagenicity bioassays to guarantee a constant surveillance on the entire regional territory. The continuous monitoring of the PM mutagenicity provides essential information for a better understanding of the impact of air pollution on the health of the population, and allows one to better judge the efficiency of national and local efforts for urban air quality improvement (use of "green" petrol and ecodiesel, days during which traffic is prohibited, etc.). This article presents the results relating to the Network's activity between September 2000 and December 2002, on PM(2.5) fraction. The organic extracts of PM(2.5) were tested for mutagenicity using Salmonella tester strains TA98 and TA100 with and without metabolic activation (S9). The data obtained on the genotoxicity of air particulate extracts have revealed a constant presence of mutagenic substances adsorbed on particulate matter-with a prevalence of direct-acting mutagens than of promutagens-in a typical seasonal trend featuring higher levels in autumn-winter and lower in warmer periods of the year. In this work the evolution of PM(2.5) mutagenicity was compared with the particles, carbon monoxide (CO) and nitrogen dioxide (NO(2)) concentrations (monthly average); these comparisons revealed a quite good level of agreement on a local basis.