Mutagenicity of the Musa paradisiaca (Musaceae) fruit peel extract in mouse peripheral blood cells in vivo

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Avaliação da eficiência da técnica de obturação pela compressão hidrùlica vertical após instrumentação automatizada

The purpose of this study was to evaluate through radiographic and microscopic analysis the efficiency of the filling techniques by vertical hidraulic compression after the root canal mechanical instrumentation in vitro as well to evaluate the marginal apical leakage through macroscopic and microscopic analysis. Thirty human mandibular molars were used , they were divided on three groups, these were subdivided on six subgroups with five specimens each, come down to 106 root canals filled. Initially, the teeth were instrumented with Profile system series 29 and filled with two ways: single accessory cone or single cone associated with gutta-percha secundary cone, with Fill Canal sealer or Sealer 26. Completed the filling, the teeth were coated with araldit and finger -nail polish except for the apical 2 mm and dried for 3 hours, thep radiographs were taken of the teeth in orto and disto-radiai directions. Next, the coronal seal was carried out with composite resin photopolymerized and with their process of making impermeable. Teeth of positive controls were used without araldit and finger-nail polish whereas the negative controls were used with total coat of araldit and finger-nail polish. The specimens were placed in 2% Methylene Blue dye for 24 hours and thermocycled for 7 days. Afterwards, sections were made of each tooth at mesial and distal roat, after this the teeth were radiographed at buccolíngual direction for a macroscopic analysis and at buccolingual and mesiodistal directions for assessment of the marginal apical leakage. Cross sections were made 3 mm to 3mm since the tooth apice. The sections obtained for each group were observed with a stereomicroscope to evaluate the quality of the root canal filling and the marginal apical leakage. The results showed that: In the four techniques the marginal dye leakage was present in the apical third; in all groups the quality of the root canal filling in the radiography was better at mesial root canal and the single cone technique showed inefficient when only a single distal root canal was present. In the radiographic evaluation the best quality of the root canal filling was observed in the 1A group (single accessory cone + FiIl Canal), as in the mesial root as in the distal root wich Shcwed twe root canals: when the distaI root had only one canal. the best result was showed by 28 group (single accessory cone associated with secundary cone + Fill Canal) In the macroscopic analysis of longitudinal !eaKage (outside surface). less leakage was showed as In the mesial root as in the distal root in the negative control group (3) followed 2A group (single accessory cone + Sealer 26). When the microscopic analysis of tranversal leakage of both roots (inside surface) was carried out. the groups that showed less dye leakage were the negative control (38) followed the 28 group (single acessory cone associated with secundary cone + Sealer 26). The homogeneity o filling was best noted in the 1 A group (.single accessoty cone + Fill Canal). The groups that showed less dye penetration in the tranversal leakage (total area) were negative control (3B) and 2B

No mutations found in exon 2 of gene p16CDKN2A during rat tongue carcinogenesis induced by 4-nitroquinoline-1-oxide

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Chlorhexidine induces DNA damage in rat peripheral leukocytes and oral mucosal cells

Objective: Chlorhexidine digluconate is widely used in dental practice for decreasing plaque control, controlling gingivitis and disinfecting root canals. However, the undesirable effects of chlorhexidine digluconate regarding its genotoxicity are conflicting in the literature. Thus, the aim of this study was to investigate the genotoxicity of chlorhexidine digluconate in rat peripheral blood and oral mucosal cells by the single cell gel (comet) assay and micronucleus assay.Methods: Thirty male Wistar rats were distributed into three groups: negative control; experimental group orally treated with 0.5 ml of 0.12% chlorhexidine digluconate, twice daily, during 8 days; and positive control, which received 4-nitroquinoline 1-oxide at 0.5 g/l by drinking water.Results: A statistically significant increase of DNA damage was observed in leukocytes and oral mucosal cells of the chlorhexidine digluconate treated group, as assessed by the comet assay. However, no increase of micronucleated cells was detected in reticulocytes from peripheral blood cells.Conclusions: Taken together, the data indicate that chlorhexidine digluconate is able to induce primary DNA damage in leukocytes and in oral mucosal cells, but no chromosome breakage or loss in erythrocytes.

Lack of effect of prior treatment with fluoride on genotoxicity of two chemical agents in vitro

The goal of this study was to investigate the ability of fluoride to modulate the genotoxic effects induced by the oxidative agent hydrogen peroxide (H2O2) and the alkylating agent methyl methanesulfonate (MMS) in vitro by the single-cell gel ( comet) assay. Chinese hamster ovary cells were exposed in culture for 1 h at 37 degrees C to sodium fluoride at 7-100 mu g/ml. NaF-treated and control cells were then incubated with 0-10 mu M MMS in phosphate-buffered saline (PBS) for 15 min at 37 degrees C, or 7-100 mu M H2O2 in distilled water for 5 min on ice. Negative control cells were treated with PBS for 1 h at 37 degrees C. Clear concentration-related effects were observed for the two genotoxins. Increase of DNA damage induced by either MMS or H2O2 was not significantly altered by pretreatment with NaF. The data indicate that NaF does not modulate alkylation-induced genotoxicity or oxidative DNA damage as measured by the single-cell gel ( comet) assay. Copyright (c) 2007 S. Karger AG, Basel

Survivin and inducible nitric oxide synthase production during 4NQO-induced rat tongue carcinogenesis: A possible relationship

This study was undertaken to investigate, by immunohistochermistry, the expression of survivin and inducible nitric oxide synthase during 4NQO-induced rat tongue carcinogenesis. Male Wistar rats were distributed into three groups of 10 animals each and treated with 50 ppm 4NQO solution through their drinking water for 4, 12, and 20 weeks. Ten animals were used as negative control. Although no histopathological abnormalities were induced in the epithelium after 4 weeks of carcinogen exposure, survivin and iNOS were expresssed (P < 0.05) in some cells of the 'normal' oral epithelium. In pre-neoplastic lesions at 12 weeks following carcinogen exposure, the levels of survivin and iNOS were increased (p < 0.05) when compared to negative control, being the strongest effect observed to iNOS. In well-differentiated squamous cell carcinoma induced after 20 weeks of treatment with 4NQO, survivin and iNOS were expressed in some tumor cells. Lack of immunoreactivity for both markers was observed in the negative control group. Taken together, our results support the belief that expression of survivin and iNOS are early events during malignant transformation and conversion of the oral mucosa. (c) 2007 Elsevier B.V. All rights reserved.

Cocaine mutagenicity and hepatocarcinogenicity evaluations in rodents

The mutagenicity (clastogenicity) and the carcinogenicity (promoting potential) of cocaine were evaluated, respectively, by the mouse bone marrow micronucleus test (study I) and by the initiated rat liver bioassay (study II). In study I, two administration routes (i.p. and i.v.) and two sampling times (24 and 48 hours) after cocaine treatment were studied. Swiss male mice were treated with cocaine at doses of 0, 18, 37, and 75 mg/kg and 0, 2, 4, and 8 mg/kg by i.p. and i.v. routes, respectively. No significant differences were observed between treated and negative control groups regarding the frequencies of micronuclei and the polichromatic/normochromatic erythrocyte (PCE/NCE) ratios. In study II, the development of putative preneoplastic foci of hepatocytes expressing the enzyme glutathione S-transferase placental form (GST-P+) was utilized as the end-point marker in a 8-week rat liver bioassay. The animals were initiated for carcinogenesis by a single i.p. sub-carcinogenic dose of diethylnitrosamine (DEN). After a 6-week exposure to 5 or 10 mg/kg of cocaine i.v. twice a week there was no enhancement of GST-P+ foci development above the values of the control DEN-only treated animals. Also, cocaine did not induce any toxicity as evidenced by the absence of alterations of rat body and liver weights and of liver biochemical function and morphology. The results suggest that cocaine does not have a mutagenic effect on the mouse bone marrow cells or promoting activity on the rat hepatocarcinogenesis process. Teratogenesis Carcinog. Mutagen. 18:199-208, 1998. (C) 1998 Wiley-Liss, Inc.

Genomic instability in non-neoplastic oral mucosa cells can predict risk during 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis

4-Nitroquinotine 1-oxide (4NQO)-induced rat tongue carcinogenesis is a useful model for studying oral squamous cell carcinoma. The aim of this study was to investigate the level of DNA damage induced by 4NQO in oral mucosa cells by the single cell get (comet) assay. Mate Wistar rats were distributed into three groups of 10 animals each and treated with 50 ppm 4NQO solution by drinking water for 4, 12 or 20 weeks. Ten animals were used as negative control. Statistically significant increase of DNA damage was observed in non-neoplastic oral cells at four weeks of 4NQO administration when compared with control (P < 0.05). The level of DNA damage was directly associated with the severity of histological changes. The results suggest that histologically normal tissue is able to harbor genetically unstable cells contributing to the initiation of oral carcinogenesis. Genomic instability appears to be associated with the risk and progression of oral cancer. (C) 2004 Elsevier Ltd. All rights reserved.

Cigarette smoke affects apoptosis in rat tongue mucosa: Role of bcl-2 gene family

While it has been clearly demonstrated that smoking is the most significant exogenous factor involved in oral carcinogenesis, little is known about the global molecular and cellular changes that occur prior to the appearance of clinically detectable symptoms. Thus, the aim of this study was to investigate the expressivity of bcl-2, bax and PCNA in the rat tongue mucosa exposed to cigarette smoke by means of immunohistochemistry. A total of twelve male Wistar rats were distributed into 2 groups: negative control and experimental group exposed to cigarette smoke during 75 days. After experimental period, no histopathological changes in the tongue mucosa were detected in the negative control and the experimental group. on the other hand, an overexpression of bcl-2 was detected (p < 0.01) throughout all layers of the epithelium, whereas bax did not show significant differences (p > 0.05). Also, the labeling index for bcl-2 and bax showed an increase 75 days after cigarette exposure (p < 0.01). PCNA-labeling index did not show remarkable changes between groups. Taken together, our results show that bcl-2 is overexpressed in the rat tongue keratinocytes after cigarette smoke exposure.

DNA damage in multiple organs after exposure to chlorhexidine in Wistar rats

Since chlorhexidine is effective against microorganisms, it is widely recommended in dentistry. However, studies have provided evidence that chlorhexidine is toxic for a variety of cell types. In order to identify potential genotoxins in different cell types, the purpose of this study was to investigate whether chlorhexidine digluconate is able to cause, in terms of DNA damage, alterations in leukocytes, liver, kidney and urinary bladder by the single cell gel (comet) assay. Ten male Wistar rats were divided into two groups: a negative control and the experimental group treated with 3 ml of 0.12% chlorhexidine digluconate by gavage once a day for 8 days. Statistically significant increases of DNA damage was observed in leukocytes and kidney cells of the chlorhexidine digluconate treated group as depicted by the mean tail moment. Taken together, the data indicate that leukocytes and kidney cells are potential targets for primary DNA damage following oral exposure to chlorhexidine digluconate as detected by single cell gel (comet) assay. (c) 2006 Elsevier GmbH. All rights reserved.

Sewage sludge does not induce genotoxicity and carcinogenesis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Imbalance of Tumor Suppression Genes Expression Following Rat Tongue Carcinogenesis Induced by 4-Nitroquinoline 1-Oxide

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Genotoxicity of corrosion eluates obtained from orthodontic brackets in vitro

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Genotoxicity in primary human peripheral lymphocytes after exposure to radiopacifiers in vitro

Taking into consideration that DNA damage plays an important role in carcinogenesis, the purpose of this study was to evaluate whether some radiopacifiers widely used in clinical practice are able to induce genetic damage in primary human cells in vitro. Human peripheral lymphocytes obtained from 10 healthy volunteers were exposed to barium sulphate (BaSO(4)), zirconium oxide (ZnO(2)) and bismuth oxide (Bi(2)O(3)) at final concentrations ranging from 1 to 1000 mu g/mL for 1 h at 37 degrees C. The negative control group was treated with vehicle control (phosphate buffer solution) for 1 h at 37 degrees C and the positive control group was treated with hydrogen peroxide (at 100 mu M) for 5 min on ice. Results were analyzed by the Friedman non-parametric test. The results pointed all compounds tested out did not induce DNA breakage in human peripheral lymphocytes as depicted by the mean tail moment and tail intensity in all concentrations tested. In summary, our results indicate that exposure to these radiopacifiers may not be a factor that increases the level of DNA lesions in human peripheral lymphocytes as detected by single cell gel (comet) assay.

Genomic instability in blood cells is able to predict the oral cancer risk: an experimental study in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)