Modulatory effect of myricitrin against chromosome instability and cytostasis induced by bleomycin and oxaliplatin in CHO-K1 cells.

Myricitrin (MYR), a flavonol consumed in the leaves and fruits of plants of the Myrtaceae family, presents anti-proliferative, anti-inflammatory, anti-diabetic, and antioxidant properties in humans. However, there are few studies regarding the cyto-genotoxicity and the chemopreventive potential of MYR. Using the in vitro Micronucleus test, the cytostasis, mutagenicity, and modulatory effect of MYR in CHO-K1 cells were assessed. The concentrations of 39 and 78 µg/mL (p < 0.001.) of MYR decrease the cytokinesis-block proliferation index (CBPI) in the short exposure treatment (4 h), while in the extended treatment (24 h), concentrations of 4.8, 9.7, 19.5, 39 and 78 µg/mL (p < 0.001.) decreased the CBPI. MYR associated with oxaliplatin decreased CBPI at all tested concentrations in the pre-(p < 0.001) and post-treatments (p < 0.001), but there was no decrease when associated with bleomycin. As for chromosome instability, MYR did not increase the frequency of micronuclei (MNi), nucleoplasmic bridges (NPBs), or nuclear buds (NBUDs) in the 4 h exposure time, however, in the 24 h treatment, MYR increased the frequency of MNi and NPBs at concentration 19.5 µg/mL (p < 0.001). As for the modulatory effect, MYR associated with bleomycin decreased the frequency of MNi, NPBs, and NBUDs at all concentrations in the pretreatment (MNi and NPBs p < 0.001, NBUDs p < 0.05) and simultaneously (MNi, NPBs and NBUDs p < 0.001). When associated with oxaliplatin, the simultaneous treatment decreased the frequency of MNi (p < 0.001) and NBUDs (p < 0.01) at all concentrations, however, in the post-treatment, MYR increased MNi (p < 0.001) and NPBs p < 0.05) in CHO-K1 cells, when compared to oxaliplatin alone. The results demonstrated that MYR could modulate the mutagenic and cytostatic actions of bleomycin and oxaliplatin, demonstrating distinct behaviors, depending on the mechanism of action of the chemotherapeutic agent.

In vitro and in silico assessment of cytotoxicity and chromosome instability induced by saxitoxin in human derived neural cell line.

In freshwater, saxitoxins (STX) are produced by different cyanobacteria genera, including Raphidiopsis. Data regarding cytogenotoxicity effects of STX on human cells are scarse, this merit further studies of its toxicology. This study assessed the cytotoxicity and the chromosome instability of STX on SHSY-5Y human cell line. The CBMN assay allows the detection of chromosome breaks and abnormal chromosomal segregation. Additionally, in silico systems biology approach, used to search for known and predicted interaction networks, was applied to study the interactions between STX and SHSY-5Y cellular components. The results of the CBMN assay demonstrated that STX concentrations of 2.5 - 10 µg/L induced cytostasis and chromosome instability in a dose-response relationship. Apoptosis was detected after exposure of SHSY-5Y cultured cells to STX concentration of 10 µg/L. The results of the systems biology analysis revealed the interaction of STX with proteins related with acetylcoline pathway, cell cycle regulation and apoptosis. Furthermore, combining the in vitro and in silico approachs, it was possible to suggest a mechanism of action of STX in SHSY-5Y cells. Overall, the data demonstrated the cytotoxicity and mutagenicity of environmentally relevant concentrations of STX. These results should be considered when setting up guidelines for monitoring STX in water supply.

Cyto-genotoxicity of crystalline and amorphous niobium (V) oxide nanoparticles in CHO-K1 cells.

Niobium (V) oxide nanoparticles (NINPs) have been widely and increasingly applied in various health products and industrial processes. This merits further study of their toxicity. Here, we investigated the potential of NINPs to induce DNA damage, cytotoxicity, and chromosome instability in cultured CHO-K1 cells. NINPs were physico-chemically characterized. As assessed by comet assay, crystalline and amorphous NINPs were genotoxic at the highest concentrations evaluated. The cytokinesis-block micronucleus assay demonstrated that a 24-h treatment with NINPs, for the crystalline and the amorphous samples, significantly reduced the nuclear division cytotoxicity index. In addition, a 4-h treatment period of crystalline NINPs increased micronucleus (MNi) frequencies. MNi, nucleoplasmic bridges and nuclear buds were detected after exposure of the cells for 24 h to crystalline NINPs. In the amorphous sample, chromosome instability was restricted to the induction of MNi, in the 24-h treatment, detected at all tested concentrations. The fluorescence and dark field microscopy demonstrated the uptake of NINPs by CHO-K1 cells and an intracellular distribution outlining the nucleus. Our data advance understanding of the cytotoxic and genotoxic effects of NINPs and should be taken into consideration when setting up guidelines for their use in industrial or health products.

In vivo and in silico approaches to assess surface water genotoxicity from Tocantins River, in the cities of Porto Nacional and Palmas, Brazil.

The main environmental problem in urban areas, especially in Brazil, is the discharge of untreated sewage. The in vivo Drosophila melanogaster Somatic Mutation and Recombination Test (SMART) was used to assess the genotoxicity of surface waters from three different sites in the Tocantins River, Brazil. The in silico approach was used to search for known and predicted interactions between environmental chemicals found in our samples and Drosophila and human proteins. The genotoxicity tests were performed in standard (ST) and high bioactivation (HB) crosses with samples collected at two periods, the rainy and dry seasons. Mutant spot frequencies found in treatments with unprocessed water from the test sites were compared with the frequencies observed in negative controls. The collection points were represented as sites A, B and C along Tocantins River. Sites A and B are located in Porto Nacional City, whereas site C is located in Palmas City. Considering the rainy season collection, positive responses in the ST cross were observed for sites A and C (89.47% and 85% of recombination, respectively) and in the HB cross for sites A, B and C (88.24%, 84.21% and 82.35% of recombination, respectively). The positive results in the dry season were restricted to sites A and B (88.89% and 85.71% of recombination, respectively) in the HB cross. In accordance with in vivo and in silico results, we hypothesize that ribosomal proteins (RPs) in fruit fly and humans are depleted in cells exposed to heavy metal causing DNA damage and chromosome instability, increasing homologous recombination.

Sarcopenia, oxidative stress and inflammatory process in muscle of cirrhotic rats - Action of melatonin and physical exercise.

Sarcopenia is one of the most common features of cirrhosis, contributing to morbidity and mortality in this population. We aimed to evaluate the effect of melatonin (MLT) and exercise (EX) on the quadriceps muscle in rats with biliary cirrhosis induced by bile duct ligation (BDL). We used 48 males (mean weight = 300 g), divided into eight groups. A 20 mg/Kg MLT dose was administered via i.p. (1 x daily), and the EX, the animals were set to swim in couples for 10 min each day. Upon completion, blood, liver, and quadriceps samples were taken for analysis. In the liver enzymes analysis and comet assay results, a reduction was observed in the groups treated with MLT with/or EX comparing to the BDL group. In the evaluation of substances that react to thiobarbituric acid (TBARS), nitric oxide levels (NO), and tumor necrosis factor-alpha levels (TNF-α), there was a significant increase in the BDL group and a reduction in the treated groups. In the activity of the superoxide dismutase enzyme (SOD) and interleukin-10 levels (IL-10) concentrations, there was a significant increase in the treated groups of the BDL group. Histological analysis revealed muscle hypotrophy in the BDL group in comparison with the control group (CO) and increased muscle mass in the treated groups. There was an increase in weight gain and phase angle in the groups treated with MLT with/or EX comparing to the BDL group. We suggest that treatments may contribute to the reduction of muscle changes in cirrhotic patients.

Assessment of complex genomic alterations induced by AZT, 3TC, and the combination AZT +3TC.

Highly active antiretroviral therapy (HAART) regimens are based on the use of nucleoside reverse transcriptase inhibitors (NRTIs), which are the main drugs used by patients infected with the human immunodeficiency virus (HIV). The use of NRTIs combinations has afforded clear clinical benefits to patients undergoing HAART. However, the combination of two NRTIs may increase the risk of genomic instability in comparison with the drugs administered individually. We analyzed the ability of zidovudine (AZT) and lamivudine (3TC), and the combination AZT +3TC to induce complex genomic alterations using the cytokinesis-block micronucleus (CBMN) assay in Chinese hamster ovary (CHO)-K1 cells. The 24-h cell treatment with individual NRTIs showed that AZT increased micronucleus frequencies and nucleoplasmic bridges (NPBs). No significant differences were observed for any parameters investigated after exposure of CHO-K1 cells to 3TC. The combination AZT +3TC significantly increased micronucleus frequencies. Analysis of interaction between these drugs suggested that antagonism occurs in all AZT +3TC concentrations. These results highlight the importance to investigate the genotoxic profile of NRTIs to develop safer intervention strategies in antiretroviral treatment protocols.

Evaluation of mutagenic activity of platinum complexes in somatic cells of Drosophila melanogaster.

Cisplatin, carboplatin, and oxaliplatin are some of the most often used alkylating chemotherapeutic agents. In view of the paucity of data on the genotoxicity of oxaliplatin, this study compares the mutagenic activity of cisplatin (0.006, 0.012, 0.025, 0.05 mM), carboplatin (0.1, 0.2, 0,5, 1.0 mM), and oxaliplatin (0.1, 0.2, 0,5, 1.0 mM) using the somatic mutation and recombination test (SMART) in Drosophila melanogaster. Standard and high-bioactivation crosses of the drosophilid were used, which present basal and high levels of cytochrome P450 (CYP450) metabolization enzymes, respectively. All concentrations of cisplatin and carboplatin induced lesions in genetic material in both crosses, while oxaliplatin was mutagenic only to high bioactivation flies treated with 0.1, 0.5 and 1 mM of the compound. No significant differences were observed between genotoxicity values of cisplatin and carboplatin. However, CYP450 enzymes may have affected the mutagenic action of oxaliplatin. Carboplatin induced mainly mutation events, while cisplatin triggered mostly mutation and recombination events when low and high doses were used. Most events induced by oxaliplatin were generated by somatic recombination. Important differences were observed in genotoxic potential of platinum chemotherapeutic compounds, possibly due to the origin and type of the lesions induced in DNA and the repair mechanisms involved.

Genotoxicity of zinc oxide nanoparticles: an in vivo and in silico study.

Zinc oxide (ZnO) NPs are being used worldwide in consumer products and industrial applications. Based on predefined pathways, this study synthesized and characterized the nanostructures of ZnO NPs. The genotoxic effects of these nanomaterials were evaluated using a short-term in vivo bioassay, the somatic mutation and recombination test (SMART) in Drosophila melanogaster. In addition, a systems biology approach was used to search for known and predicted interaction networks between ZnO and proteins. The results observed in this study after in vivo exposure indicate that ZnO NPs are genotoxic and that homologous recombination (HR) was the main mechanism inducing loss of heterozygosis in the somatic cells of D. melanogaster. The results of in silico analysis indicated that ZnO is associated with the nuclear factor-kappa-beta (NFKB) protein family. In accordance with this model, ZnO exposure decreases the levels of NFKB inhibitory protein in the cell, consequently increasing NFKB dimers in the nucleus and inducing DNA double strand breaks (DSB) repair via HR. This excess level of HR can be observed in the SMART results. Assessing the mutagenic/recombinagenic effect of nanomaterials is essential in the development of strategies to protect human and environmental integrity.

Evaluation of the genotoxic properties of nickel oxide nanoparticles in vitro and in vivo.

Nickel-based nanoparticles (NPs) are new products with an increasing number of industrial applications that were developed in recent years. NiO NPs are present in several nanotechnological industrial products, and the characterization of their genotoxic potential is essential. The present study assessed the genotoxicity of NiO NPs in vivo and in vitro using the somatic mutation and recombination test in somatic cells of Drosophila melanogaster (SMART), the cytokinesis - block micronucleus assay (CBMN), and the comet assay in a V79 cell line. The NiO NPs used in this study were about 30 nm in mean size. Larvae of Drosophila melanogaster were exposed to 5 mL of five different concentrations (1.31, 2.62, 5.25, 10.5, and 21 mg/mL) of NiO NPs. In turn, V79 cells were treated with a concentration range of 15-2000 µg/mL NiO NPs. The SMART showed that all concentrations of NiO NPs are genotoxic to the standart (ST) cross when compared to the negative control. On the other hand, only the highest concentration (21 mg/mL) was genotoxic to the HB cross. Somatic recombination was the preferential mechanism lesions were induced in D. melanogaster. The results show that NiO NPs were mutagenic to V79 cells as assessed by the CBMN assay. Significant differences in the frequencies of micronuclei (MN) were observed using the highest NiO NP concentrations (250 and 500 µg/mL) in the 4- and 24-h treatments, but when 125 µg/mL NiO NPs was used, such difference was observed only in the 4-h exposure time. The comet assay revealed that 62, 125, 250 and 500 µg/mL NiO NPs induced a significant increase in DNA damage. The results observed in this study indicate that NiO NPs are genotoxic and mutagenic in vitro and in vivo.

In Vivo Analysis of Photobiomodulation Genotoxicity Using the Somatic Mutation and Recombination Test.

BACKGROUND: Photobiomodulation (PBM) has been studied mainly for its effects on the repair, regeneration, and healing of tissue due to its direct and indirect actions on cell proliferation. However, it is necessary to consider the way in which laser acts, that is, whether it affects the rates of spontaneous mutation and mitotic recombination of cells. OBJECTIVE: This study investigated the genotoxic potential of PBM (904 nm) based on an in vivo bioassay that concomitantly evaluates mitotic recombination and point and chromosomal mutations. METHODS: Strains of Drosophila melanogaster that carry specific marker genes were used to detect the induction of mutation and somatic recombination when exposed to different fluences (3, 5, 10, and 20 J/cm2). DNA damage was measured using the somatic mutation and recombination test (SMART), which is based on the identification of wing hair with mutant phenotypes that express lesions at DNA level. RESULTS: The doses 5, 10, and 20 J/cm2 induced significant increase in the total number of spots compared with the negative control. The highest frequency of spots was caused by the 10 J/cm2. CONCLUSIONS: Besides recombination events, the quantitative and qualitative analysis of mutant hairs revealed the occurrence of mutagenic events, both punctual and chromosomal. In addition, the results point to a dose-dependent response.

Genotoxic and chemopreventive assessment of Cynara scolymus L. aqueous extract in a human-derived liver cell line.

Cynara scolymus L., popularly known as artichoke, is consumed as food and used as tea infusions for pharmacological purposes to treat liver dysfunctions and other conditions. Scientific data on the safety and protective effect of artichoke in human-derived liver cells is missing. This study investigated the genotoxic and modulatory effect of a liophilized extract suspended in water of C. scolymus L. leaves. Four extract concentrations (0.62, 1.25, 2.5 and 5.0 mg/mL) were evaluated using the comet assay on human hepatocyte cultures, HepG2 cells. Genotoxicity was assessed after two treatment periods, 1 and 24 h. Antigenotoxicity was evaluated against oxidative lesions induced by hydrogen peroxide in pre-, simultaneous and post-treatment protocols. Artichoke leaves aqueous extract induced genotoxic effects in HepG2 cells after 1- and 24-h treatments. In turn, extract concentrations of 0.62, 1.25 and 2.5 mg/mL, exhibited a protective effect in pretreatment, compared to hydrogen peroxide alone. However, in simultaneous and post-treatment protocols, only the lowest concentration reduced the frequency of DNA damage induced by hydrogen peroxide. In addition, in the simultaneous treatment protocol, the highest artichoke extract concentration increased hydrogen peroxide genotoxicity. It can be concluded that artichoke is genotoxic, in vitro, to HepG2 cells, but can also modulate hydrogen peroxide DNA damage.

Cytotoxic, genotoxic and mutagenic evaluation of surface waters from a coal exploration region.

Coal mining generates a considerable amount of waste, which is disposed of in piles or dams near mining sites. As a result, leachates may reach rivers and streams, promoting the wide dispersion of contaminants in solution and as particulate matter. The present study evaluated the cytotoxic, genotoxic, and mutagenic action of surface waters collected around a thermoelectric power plant and the largest mining area in Brazil (Candiota). Four sites in Candiota stream were selected, and samples were collected in winter and summer. Water samples were analyzed using the comet and CBMN assays in V79 and HepG2 cells. Furthermore, genotoxicity of water samples was evaluated in vivo using the SMART in Drosophila melanogaster. In addition, polycyclic aromatic hydrocarbons and inorganic elements were quantified. The results indicate that water samples exhibited no genotoxic and mutagenic activities, whether in vitro or in vivo. On the other hand, surface water samples collected in sites near the power plant in both summer and winter inhibited cell proliferation and induced increased frequencies of V79 cell death, apoptosis, and necrosis. The cytotoxicity observed may be associated with the presence of higher concentration of inorganic elements, especially aluminum, silicon, sulfur, titanium and zinc at sites 1 and 2 in the stream, as well as with the complex mixture present in the coal, in both seasons. Therefore, the results obtained point to the toxicity potential of water samples with the influence of coal mining and combustion processes and the possible adverse effects on the health of exposed organisms.

Assessment of genotoxic and antigenotoxic activities of artepillin C in somatic cells of Drosophila melanogaster.

The significant contents of artepillin C (AC) in green propolis have prompted research on the biological activities of the compound. The present study evaluated the activity of this phenolic compound on DNA, assessing its genotoxic and antigenotoxic potentials in the somatic mutation and recombination test in Drosophila melanogaster. The standard (ST) and high-bioactivation (HB) crosses were used in the assessment of genotoxic potential, since they express cytochrome P450 metabolization enzymes differently. In the 0.1-1.6 mM concentration range, AC did not have any genotoxic action in either cross. Antigenotoxic potential was investigated using the ST cross. In co- and post-treatment protocols, AC 0.4, 0.8, and 1.6 mM did not modulate mutagenic action of ethyl methanesulphonate. However, though it did not influence the frequency of damage induced by mitomycin C in co-treatment, AC reduced genotoxicity of the mutagen when administered after damage, but only at 0.4 mM. This modulation is associated with the reduction of genetic damage caused by recombinational events. The results of the present study and literature findings indicate that the various responses elicited by AC, namely induction of DNA damage, production of genetic lesions, or activation of DNA repair mechanisms are functions of AC concentration.

Comparative study on the induction of complex genomic alterations after exposure of mammalian cells to carboplatin and oxaliplatin.

Metal complexes are still broadly used as the first line of the treatment for different types of tumors nowadays. Carboplatin and oxaliplatin were authorized for clinical use, even though there is little information on the mutagenic profile associated to their usage. This study evaluated the cytostatic effects and the induction of complex genomic alterations after 24-h treatment of CHO-K1 cells to concentrations of 12.5-800 µM of carboplatin and oxaliplatin in the cytokinesis-block micronucleus assay (CBMN-Cyt). The results demonstrated that carboplatin and oxaliplatin significantly increased the frequency of micronuclei (MN), nucleoplasmatic bridges (NPBs), and nuclear buds (NBUDs). On one hand, oxaliplatin induces significantly more chromosomal abnormalities than carboplatin at concentrations of 12.5 and 25 µM. On the other hand, carboplatin, in cells exposed to concentrations of 50 and 100 µM, is more efficient than oxaliplatin in the induction of chromosomal instability events. Both drugs cause significant reduction in the cytokinesis-block proliferation index, demonstrating their cytostatic effects at concentrations 50-800 µM. The results of this study shed more light on the characterization of biological effects associated with the exposure to carboplatin and oxaliplatin.

Surface Water Impacted by Rural Activities Induces Genetic Toxicity Related to Recombinagenic Events in Vivo.

This investigation assessed the interaction of surface water samples with DNA to quantitatively and qualitatively characterize their mutagenic and/or recombinagenic activity. Samples were obtained at three different sites along the Tocantins River (Tocantins State, Brazil). The area has withstood the impact mainly of rural activities, which release different chemical compounds in the environment. The Drosophila melanogaster Somatic Mutation and Recombination Test (SMART) was performed in standard (ST) and high bioactivation (HB) crosses. SMART is useful for the detection of mutational and recombinational events induced by genotoxins of direct and indirect action. Results demonstrated that samples collected in both seasons were able to induce increments on the mutant spot frequencies in the larvae of the HB cross. Genotoxicity was related to a massive recombinagenic activity. The positive responses ascribed to only the HB cross means that it is linked to pro-genotoxins requiring metabolic activation. The SMART wing test in Drosophila melanogaster was shown to be highly sensitive to detect genotoxic agents present in the aquatic environment impacted by agriculture.

DNA damage protective effect of honey-sweetened cashew apple nectar in Drosophila melanogaster.

Fruits and derivatives, such as juices, are complex mixtures of chemicals, some of which may have mutagenic and/or carcinogenic potential, while others may have antimutagenic and/or anticancer activities. The modulating effects of honey-sweetened cashew apple nectar (HSCAN), on somatic mutation and recombination induced by ethyl methanesulfonate (EMS) and mitomycin C (MMC) were evaluated with the wing spot test in Drosophila melanogaster using co- and post-treatment protocols. Additionally, the antimutagenic activity of two HSCAN components, cashew apple pulp and honey, in MMC-induced DNA damage was also investigated. HSCAN reduced the mutagenic activity of both EMS and MMC in the co-treatment protocol, but had a co-mutagenic effect when post-administered. Similar results were also observed with honey on MMC mutagenic activity. Cashew apple pulp was effective in exerting protective or enhancing effects on the MMC mutagenicity, depending on the administration protocol and concentration used. Overall, these results indicate that HSCAN, cashew apple and honey seem capable of modulating not only the events that precede the induced DNA damages, but also the Drosophila DNA repair processes involved in the correction of EMS and MMC-induced damages.

In vivo evaluation of mutagenic and recombinagenic activities of Brazilian propolis.

Propolis is a resinous, complex mixture of compounds collected by the bee species Apis mellifera. This study investigated the genotoxicity of green and brown propolis collected in southeast Brazil using the somatic mutation and recombination test (SMART) in Drosophila melanogaster. The effect of five concentrations (0.5, 1.0, 2.0, 4.0, and 7.5 mg/mL) of both propolis types was analyzed in standard (ST) and high-bioactivation (HB) crosses, which have normal and high levels of cytochrome P450 enzymes, respectively. The results show that the types of propolis evaluated have no mutagenic action, in either cross. Moreover, chromatography findings revealed that the propolis types analyzed have different chemical compositions. Brown propolis had lower levels of polyphenols (∼7.2 mg/mL), compared to the green type (34.9 mg/g). Taken together, the findings of the present study and literature reports point to the safety in consuming low amounts of propolis, considering the risk of genetic damage, and confirm the absence of mutagenic and recombinagenic actions of the propolis types investigated.

Occupational exposure of workers to pesticides: Toxicogenetics and susceptibility gene polymorphisms.

Farm workers are often exposed to pesticides, which are products belonging to a specific chemical group that affects the health of agricultural workers and is mostly recognized as genotoxic and carcinogenic. The exposure of workers from Piauí, Brazil, to these hazardous chemicals was assessed and cytogenetic alterations were evaluated using the buccal micronucleus assay, hematological and lipid parameters, butyrylcholinesterase (BChE) activity and genetic polymorphisms of enzymes involved in the metabolism of pesticides, such as PON1, as well as of the DNA repair system (OGG1, XRCC1 and XRCC4). Two groups of farm workers exposed to different types of pesticides were evaluated and compared to matched non-exposed control groups. A significant increase was observed in the frequencies of micronuclei, kariorrhexis, karyolysis and binucleated cells in the exposed groups (n = 100) compared to controls (n = 100). No differences were detected regarding the hematological parameters, lipid profile and BChE activity. No significant difference was observed either regarding DNA damage or nuclear fragmentation when specific metabolizing and DNA repair genotypes were investigated in the exposed groups.

Geosmin induces genomic instability in the mammalian cell microplate-based comet assay.

Geosmin (GEO) (trans-1,10-dimethyl-trans-9-decalol) is a metabolite that renders earthy and musty taste and odor to water. Data of GEO genotoxicity on mammalian cells are scarce in the literature. Thus, the present study assessed the genotoxicity of GEO on Chinese hamster ovary (CHO) cells in the microplate-based comet assay. The percent of tail DNA (tail intensity (TI)), tail moment (TM), and tail length (TL) were used as parameters for DNA damage assessment. The results demonstrated that concentrations of GEO of 30 and 60 µg/mL were genotoxic to CHO cells after 4- and 24-h exposure periods, in all parameters evaluated, such as TI, TM, and TL. Additionally, GEO 15 µg/mL was genotoxic in the three parameters only in the 24-h exposure time. The same was observed for GEO 7.5 µg/mL, which induced significant DNA damage observed as TI in the 24-h treatment. The results present evidence that exposure to GEO may be associated with genomic instability in mammalian cells.

Agents of earthy-musty taste and odor in water: evaluation of cytotoxicity, genotoxicity and toxicogenomics.

Considering the limited number of studies on the biological effects on human health of cyanobacterial compounds that cause taste and odor, the present study assessed the cytotoxic and genotoxic potentials of 2-methylisoborneol (2-MIB) and geosmin (GEO) using the MTT assay and the in vitro comet and cytokinesis-block micronucleus (CBMN-Cyt) assays in human HepG2 cells. The toxicogenomics of genes responsive to DNA damage and metabolization by the exposure of cells to 2-MIB and GEO were also investigated. The results showed that concentrations of 2-MIB and GEO above 100 and 75 µg/mL, respectively, were cytotoxic to HepG2 cells. Doses of 2-MIB (12.5, 25, 50, 75 and 100 µg/mL) and GEO (12.5, 25, 50, and 75 µg/mL) were unable to induce neither DNA damage nor events associated with chromosomal instability. Similarly, no concentration of each compound induced increments in the expression of CDKN1A, GADD45α, MDM2 and TP53 DNA damage responsive genes as well as in CYP1A1 and CYP1A2 metabolizing genes. Although cytotoxicity was observed, concentrations that caused it are much higher than those expected to occur in aquatic environments. Thus, environmentally relevant concentrations of both compounds are not expected to exhibit cytotoxicity or genotoxicity to humans.