In vivo experimental study to investigate cytogenotoxicity of a contaminated estuary from Southeastern Brazilian Coast.

The aim of this study was to evaluate cytogenotoxicity in mammalian cells induced by ingestion of superficial water from SESS. For this purpose, surface water was collected from two points of SESS: São Vicente Channel (SVC) and Piaçaguera Channel (PIC). Four groups (n = 5) of adult male Wistar (8 weeks old) received for 5 days: (a) filtered tap water (water control), (b) tap water with 2.4% of NaCl (saline control), (c) estuarine water from PIC and (d) estuarine water from SVC. Results demonstrated that Ki67 immunoexpression was higher in hepatocytes exposed to both sampling site, while caspase-3 demonstrated downregulation in rat liver exposed to estuarine water. There was also significant increase in micronuclei frequency in bone marrow cells and hepatocytes, and DNA damage in blood and liver of rats exposed to estuarine water from SVC and PIC. In summary, studies with complex mixtures, such as contaminated estuarine water are important since this work confirmed by experiments using in vivo mammalian cells of rats that SESS water are genotoxic, mutagenic and cytotoxic, denoting concern for environmental health.

Genomic Instability in Buccal Mucosal Cells of Municipal Street Sweepers as Evaluated by Micronucleus Test.

BACKGROUND/AIM: Since street sweepers comprises a group of workers who are in daily contact with rubbish, dust and air pollution, the aim of this study was to evaluate potential cytotoxic and mutagenic effects in buccal mucosa cells of street sweepers. MATERIALS AND METHODS: A total of 20 male street sweepers aged from 22 to 56 years were included in the experimental group. A total of 20 men matched by age were used as the control group. Cytotoxicity and mutagenicity were analyzed by micronucleus test in buccal mucosal cells. RESULTS: Statistically significant differences (p<0.05) in the frequency of micronuclei was detected in the street sweepers when compared to the control group. No remarkable differences were found to other metanuclear alterations indicative for cytotoxicity such as pyknosis, karyolysis, and karryorhexis when compared to matched controls. CONCLUSION: Taken together, our results indicate that street sweepers comprise an at-risk group as a result of increased mutagenicity found to buccal mucosa cells.

Physico-chemical characterization and biocompatibility of hydroxyapatite derived from fish waste.

The aim of this study was to synthesize hydroxyapatite (HAP) powder from fish waste. The powder was characterized through X-ray diffraction, Fourier transform infrared spectroscopy, ion exchange chromatography, scanning electron microscopy and plasma emission spectrometry. The cyto- and genotoxicity was carried out to demonstrate biocompatibility in vivo by means of rat subcutaneous tissue test. The results showed that the visible crystalline nature of typical apatite crystal structure when they were calcined at 800 °C. Infrared spectroscopy analysis showed similar composition to HAP standard with the presence of carbonate ion demonstrated by wave number values of 871 cm-1 and 1420 cm-1 for calcinations at 800 °C. The scanning electronmicrographies depicted the crystal morphology and porous nature with average pore size of ~10 µm. Plasma emission spectrometry and ion exchange chromatography confirmed the presence of Ca and P in the samples. The mean of calcium content was 36.8; Mg was 0.8, Na was 0.7 and K was 0.5. Rat subcutaneous tissue test revealed that HAP presented biocompatibility. Furthermore, the lack of cyto- and genotoxicity in blood, liver, kidney and lung were noticed after 30 days of HAP implantation. Taken together, our results demonstrated that HAP from fish waste exhibits a great potential for using as biomaterial since is represents a simple, effective, low-cost process and satisfactory degree of biocompatibility.

Putative mechanisms of genotoxicity induced by fluoride: a comprehensive review.

Genotoxicity is the ability of an agent to produce damage on the DNA molecule. Considering the strong evidence for a relationship between genetic damage and carcinogenesis, to elucidate the putative mechanisms of genotoxicity induced by fluoride are important to measure the degree of risk involved to human populations. The purpose of this article is to provide a comprehensive review on genotoxicity induced by fluoride on the basis of its mechanisms of action. In the last 10 years, all published data showed some evidence related to genotoxicity, which is due to mitochondrial disruption, oxidative stress, and cell cycle disturbances. However, this is an area that still requires a lot of investigation since the published data are not sufficient for clarifying the genotoxicity induced by fluoride. Certainly, the new information will be added to those already established for regulatory purposes as a safe way to promote oral healthcare and prevent oral carcinogenesis.

Evaluation of genotoxic and cytotoxic effects in buccal mucosa cells of welders in the cities of Cubatão and Santos, state of São Paulo, Brazil.

BACKGROUND: Approximately 5 million workers are estimated to be occupationally exposed to welding fumes worldwide. Nickel and chromium are genotoxic metals found in welding fumes, therefore welders are exposed to these metals at the workplace. OBJECTIVE: The objective of the present study was to investigate the frequency of cytotoxic and genetic damage in cells harvested from the oral mucosa of welders and also from a group of workers not exposed to metallic fumes. METHODS: A total of 44 individuals, divided into 2 groups - welders and non-welders - were compared using the micronucleus assay technique and cell death (pyknosis, karyorrhexis and karyolysis) on buccal mucosa cells of welding workers. The examined cells were stained with Feulgen/Fast Green. Results: Welders exhibited higher frequency (p<0.05) of cytotoxicity than the group of volunteers not exposed to metallic fumes. CONCLUSION: The results of this preliminary study suggest that the frequency of cytotoxic damage in buccal mucosa cells might be higher among welders compared to non-welders.

CONTEXTO: Estima-se que no mundo existam, aproximadamente, 5 milhões de trabalhadores expostos ocupacionalmente à fumaça de soldagem. Níquel e Cromo são metais que podem ocasionar danos ao material genético, e soldadores, por força do ofício, são rotineiramente expostos a eles. OBJETIVO: O objetivo do presente estudo foi investigar a frequência de danos citotóxicos e genotóxicos em células da mucosa bucal de um grupo de soldadores. MÉTODOS: Um total de 44 indivíduos, distribuídos em 2 grupos - soldadores e não soldadores -, foi comparado utilizando a técnica do ensaio do micronúcleo e morte celular (picnose, cariorrexe e cariólise) em células da mucosa oral de trabalhadores de soldagem. As células examinadas foram coradas com Feulgen/Fast-green. RESULTADO: Os soldadores apresentaram maior frequência (p<0,05) de alterações indicativas de citotoxicidade quando comparados ao grupo de indivíduos não expostos a fumos metálicos. CONCLUSÃO: Os resultados deste estudo preliminar sugerem que soldadores apresentam maior frequência de danos citotóxicos e morte celular em células da mucosa bucal que trabalhadores não expostos.

Genotoxicity, mutagenicity and cytotoxicity of carotenoids extracted from ionic liquid in multiples organs of Wistar rats.

The ionic liquid or melted salt 1-Butyl-3-methylimidazolium is an alternative process to extract natural pigments, such as carotenoids. Lycopene represents 80-90% of total of carotenoids presents in tomatoes and it has been widely studied due its potent antioxidant action. The aim of this study was to evaluate genotoxicity, mutagenicity and cytotoxicity of carotenoids extracted from ionic liquid using experimental model in vivo. For this purpose, a total of 20 male Wistar rats were distributed into four groups (n=5), as follows: control group; received a corresponding amount of corn oil for 7days by intragastric gavage (i.g.), ionic liquid group, received 10mgkg-1 body weight for 7days by gavage; 10mg carotenoids group, received 10mgkg-1 bw dissolved in corn oil for 7days by gavage and 500mg carotenoids group, received 500mgkg-1 bw dissolved in corn oil for 7days by gavage. Rat liver treated with ionic liquid exhibited moderate histopathological changes randomly distributed in the parenchyma, such as cytoplasmic eosinophilia, apoptotic bodies, inflammatory infiltrate and focal necrosis. DNA damage was found in peripheral blood and liver cells of rats treated with ionic liquid or carotenoids at 500mg. An increase of micronucleated cells and 8-OhDG immunopositive cells were also detected in rats treated with carotenoids at 500mg. In summary, our results demonstrate that recommended dose for human daily intake of carotenoids extracted by ionic liquid did not induce genotoxicity, mutagenicity and cytotoxicity in multiple organs of rats.

Cytogenetic Biomonitoring in Buccal Mucosa Cells from Women Submitted to Chemotherapy After Mastectomy for Breast Cancer.

In addition to surgery, one of the most widely applied treatments for breast cancer is chemotherapy. Chemotherapy is currently considered efficient in curing this disease; however, the therapy may induce damage to the patient's genetic material. Thus, the aim of this study was to evaluate putative cytotoxic and mutagenic effects induced by chemotherapy in women diagnosed with breast cancer. For this purpose, a cross-sectional study was carried out in 42 women, aged 18 to 70 years, allocated according to the diagnosis and stage of breast cancer treatment: control group (healthy) (n=15), chemotherapy group (n=11) and post-chemotherapy group (n=16). Cytotoxicity and mutagenicity were analyzed by the micronucleus test in buccal mucosa cells. A higher frequency (p<0.05) of micronucleated cells was detected in the chemotherapy and post-chemotherapy groups when compared to the control. A higher frequency (p<0.05) of karyorrhexis and pyknosis in the chemotherapy group was also noted. Taken together, our results indicate that chemotherapy induces mutagenicity and cytotoxicity in buccal mucosa cells of women diagnosed with breast cancer, being persistent after finishing their treatment.

Mimosa (Mimosa caesalpiniifolia) prevents oxidative DNA damage induced by cadmium exposure in Wistar rats.

The Mimosa (Mimosa caesalpiniifolia) is a plant native from South America; it is used in the traditional medicine systems for treating bacterial, fungal, parasitic and inflammatory conditions. The aim of this study was to evaluate the antigenotoxic and antioxidant activities induced by mimosa (M. caesalpiniifolia) in multiple rodent organs subjected to intoxication with cadmium chloride. A total of 40 Wistar rats (8 weeks old, 250 g) were distributed into eight groups (n = 5), as follows: Control group (non-treated group, CTRL); Cadmium exposed group (Cd); cadmium exposure and treated with extract at 62.5 mg/kg/day; cadmium exposure and treated with extract at 125 mg/kg/day; cadmium exposure and treated with extract at 250 mg/kg/day; cadmium exposure and treated with ethyl acetate fraction at 62.5 mg/kg/day. For evaluating the toxicogenetic potential of mimosa, two groups were included in the study being treated with extract at 250 mg/kg/day and acetate fraction of mimosa at 62 mg/kg/day, only. Extract of mimosa at concentrations of 62.5 and 125 mg decreased DNA damage in animals intoxicated with cadmium when compared to cadmium group. In a similar manner, treatment with ethyl acetate fraction of mimosa at 62.5 mg concentration in animals previously exposed to cadmium reduced genetic damage in peripheral blood cells. In a similar manner, the treatment with ethyl acetate fraction reduced DNA damage in liver cells. Oxidative DNA damage was reduced to animals exposed to cadmium and treated with 125 mg of extract as well as those intoxicated to cadmium and treated with 62.5 of acetate fraction of mimosa. Taken together, our results indicate that mimosa prevents genotoxicity induced by cadmium exposure in liver and peripheral blood cells of rats as a result of antioxidant activity.

Antimutagenic and antigenotoxic potential of grape juice concentrate in blood and liver of rats exposed to cadmium.

The aim of this study was to evaluate the antimutagenic and antigenotoxic potential of grape juice concentrate in rodent organs exposed to cadmium chloride intoxication. A total of 15 Wistar rats were distributed into three groups (n = 5), as follows: control group (CTRL; nontreated group), cadmium group (Cd), and cadmium-grape juice group (Cd + GJ). Exposed animals received intraperitoneal injection of cadmium chloride (1.2 mg/kg body weight) diluted in water and, after 15 days, Cd + GJ group received grape juice concentrate for 15 days, by gavage (0.8 mL, 1.18 mg of polyphenols kg(-1) day(-1)). Grape juice concentrate was able to decrease genotoxic effects induced by cadmium in peripheral blood and liver cells as depicted by single cell gel (comet) and micronucleus assays. A decrease for anti-8-hydroxy-20-deoxyguanosine (8OHdG) expression in hepatocytes of animals exposed to cadmium and treated with grape juice concentrate was also detected. Higher CuZn-SOD activity was observed in liver cells of the Cd + GJ group. No remarkable differences were seen regarding Mn-SOD activity among groups. Taken together, our results demonstrate that grape juice concentrate was able to exert antimutagenic and antigenotoxic activities in blood and liver cells of rats exposed to cadmium.

Genotoxicity and cytotoxicity induced by municipal effluent in multiple organs of Wistar rats.

The aim of this study was to evaluate cytotoxicity and genotoxicity in multiple organs of rats induced by municipal effluent released by submarine outfall in city of Santos. A total of 20 male Wistar rats were exposed to effluents by drinking water ad libitum at concentrations of 0, 10, 50, and 100 % for 30 days. Microscopic analysis revealed severe lesions such as necrosis and hemorrhagic areas in liver and kidney from animals exposed to effluent at 50 and 100 % concentration. DNA damage in peripheral blood, liver, and kidney cells were detected by comet assay at higher concentrations of effluent. Moreover, a decrease DNA repair capacity was detected in liver cells. Significant statistical differences (p<0.05) for micronucleated cells from liver were noticed at 50 % concentration of effluent. Taken together, our results demonstrate that municipal effluent is able to induce cytotoxicity and genotoxicity in multiple organs of Wistar rats.

Cytogenetic biomonitoring of oral mucosa cells of crack cocaine users.

The aim of the present study was to comparatively evaluate genomic damage (micronucleus) and cellular death (pyknosis, karyolysis, and karyorrhexis) in exfoliated oral mucosa cells from crack cocaine users by micronucleus test. A total of 30 crack cocaine users and 30 health controls (non-exposed individuals) were included in this setting. Individuals had epithelial cells from cheek mechanically exfoliated, placed in fixative, and dropped in clean slides, which were checked for the above nuclear phenotypes. The results pointed out significant statistical differences (p < 0.05) of micronucleated oral mucosa cells from crack cocaine users. Exposure to crack cocaine caused an increase of other nuclear alterations closely related to cytotoxicity such as karyolysis in oral cells as well. In summary, these data indicate that crack cocaine is able to induce chromosomal breakage and cellular death in oral mucosa cells of users.

Biocompatibility of a porous alumina ceramic scaffold coated with hydroxyapatite and bioglass.

This study aimed to evaluate the osteointegration and genotoxic potential of a bioactive scaffold, composed of alumina and coated with hydroxyapatite and bioglass, after their implantation in tibias of rats. For this purpose, Wistar rats underwent surgery to induce a tibial bone defect, which was filled with the bioactive scaffolds. Histology analysis (descriptive and morphometry) of the bone tissue and the single-cell gel assay (comet) in multiple organs (blood, liver, and kidney) were used to reach this aim after a period of 30, 60, 90, and 180 days of material implantation. The main findings showed that the incorporation of hydroxyapatite and bioglass in the alumina scaffolds produced a suitable environment for bone ingrowth in the tibial defects and did not demonstrate any genotoxicity in the organs evaluated in all experimental periods. These results clearly indicate that the bioactive scaffolds used in this study present osteogenic potential and still exhibit local and systemic biocompatibility. These findings are promising once they convey important information about the behavior of this novel biomaterial in biological system and highlight its possible clinical application.

Metastasis from oral cancer: an overview.

Oral cancer is a common neoplasm worldwide. Its incidence and mortality have also increased over the past decades. It is characterized by poor prognosis and a low survival rate despite sophisticated surgical and radiotherapeutic modalities. Metastasis of oral cancer is a complex process involving detachment of cells from tumor tissue, regulation of cell motility and invasion, proliferation and evasion through the lymphatic system or blood vessels. In this review, we will focus on the current knowledge in metastasis from oral cancer regarding facts, such as incidence; stage, histopathology and grade of primary tumor; clinical manifestations; diagnosis; and treatment. Certainly, such information will contribute to the understanding of oral cancer pathogenesis.

Acute spinal cord injury induces genetic damage in multiple organs of rats.

Spinal cord injury (SCI) is a devastating condition with important functional and psychological consequences. However, the underlying mechanisms by which these alterations occur are still not fully understood. The aim of this study was to analyze genomic instability in multiple organs in the acute phase of SCI by means of single cell gel (comet) assay. Rats were randomly distributed into two groups (n = 5): a SHAM and a SCI group killed 24 h after cord transection surgery. The results pointed out genetic damage in blood cells as depicted by the tail moment results. DNA breakage was also detected in liver and kidney cells after SCI. Taken together, our results suggest that SCI induces genomic damage in multiple organs of Wistar rats.

Grape juice concentrate modulates p16 expression in high fat diet-induced liver steatosis in Wistar rats.

PURPOSE: The goal of this study was to investigate whether subchronic treatment with grape juice concentrate is able to protect the liver from high fat diet injury in rats. The effects of grape juice concentrate treatment on histopathological changes, and immunohistochemistry for p53, p16 and p21 were evaluated. METHODS: Male Wistar rats (n = 18) were distributed into three groups: group 1: negative control; group 2: cholesterol at 1% (w/w) in their diet, treated during 5 weeks; and group 3: cholesterol at 1% in their chow during 5 weeks, and grape juice concentrate at 222 mg per day in their drinking-water in the last week only. RESULTS: The results pointed out that treatment with grape juice concentrate did not show remarkable differences regarding liver tissue in the cholesterol-exposed group when compared to group 2. However, grape juice concentrate was able to modulate p16 immunoexpression when compared to high fat diet group. p53 and p21 did not show any significant statistical differences among groups. CONCLUSION: Taken together, our results suggest that subchronic grape juice concentrate administration was able to modulate cell cycle control by downregulation of p16 immunoexpression in high fat diet-induced liver steatosis in rats.