Ensaios imunoenzimáticos (ELISA) para detecção da resposta sorológica contra Salmonella Gallinarum, Salmonella Pullorum, Salmonella Enteritidis e Salmonella Typhimurium em aves

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

Avaliação de genotoxicidade e estresse oxidativo em profissionais recém-expostos aos resíduos de gases anestésicos

Pós-graduação em Cirurgia Veterinária - FCAV

Alterações genéticas relacionadas à obesidade: danos no DNA, perfil de expressão e polimorfismos gênicos

Pós-graduação em Patologia - FMB

Estudo do potencial genotóxico da Gutiferona A em diferentes células de camundongos in vitro

Pós-graduação em Biologia Geral e Aplicada - IBB

DNA damage and antioxidant status in medical residents occupationally exposed to waste anesthetic gases

PURPOSE:To investigate the effects of occupational exposure to waste anesthetic gases on genetic material and antioxidant status in professionals during their medical residency. METHODS:The study group consisted of 15 medical residents from Anesthesiology and Surgery areas, of both genders, mainly exposed to isoflurane and to a lesser degree to sevoflurane and nitrous oxide; the control group consisted of 15 young adults not exposed to anesthetics. Blood samples were drawn from professionals during medical residency (eight, 16 and 22 months of exposure to waste anesthetic gases). DNA damage was evaluated by comet assay, and antioxidant defense was assessed by total thiols and the enzymes glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT). RESULTS:When comparing the two groups, DNA damage was significantly increased at all time points evaluated in the exposed group; plasma thiols increased at 22 months of exposure and GPX was higher at 16 and 22 months of exposure. CONCLUSION:Young professionals exposed to waste anesthetic gases in operating rooms without adequate scavenging system have increased DNA damage and changes in redox status during medical residency. There is a need to minimize exposure to inhalation anesthetics and to provide better work conditions.

Compounds used to produce cloned animals are genotoxic and mutagenic in mammalian assays in vitro and in vivo

The compounds 6-dimethylaminopurine and cycloheximide promote the successful production of cloned mammals and have been used in the development of embryos produced by somatic cell nuclear transfer. This study investigated the effects of 6-dimethylaminopurine and cycloheximide in vitro, using the thiazolyl blue tetrazolium bromide colorimetric assay to assess cytotoxicity, the trypan blue exclusion assay to assess cell viability, the comet assay to assess genotoxicity, and the micronucleus test with cytokinesis block to test mutagenicity. In addition, the comet assay and the micronucleus test were also performed on peripheral blood cells of 54 male Swiss mice, 35 g each, to assess the effects of the compounds in vivo. The results indicated that both 6-dimethylaminopurine and cycloheximide, at the concentrations and doses tested, were cytotoxic in vitro and genotoxic and mutagenic in vitro and in vivo, altered the nuclear division index in vitro, but did not diminish cell viability in vitro. Considering that alterations in DNA play important roles in mutagenesis, carcinogenesis, and morphofunctional teratogenesis and reduce embryonic viability, this study indicated that 6-dimethylaminopurine and cycloheximide utilized in the process of mammalian cloning may be responsible for the low embryo viability commonly seen in nuclear transfer after implantation in utero.

Avaliação dos efeitos deletérios do diuron e de seus metabólitos em lambaris (Astyanax sp.): testes de toxicidade, marcadores de estresse oxidativo, marcadores genotóxicos e enzimas de biotransformação

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

(S)-Goniothalamin induces DNA damage, apoptosis, and decrease in BIRC5 messenger RNA levels in NCI-H460 cells

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Benzophenone guttiferone A from Garcinia achachairu Rusby (Clusiaceae) Presents Genotoxic Effects in Different Cells of Mice

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

Genotoxic assessment of Rubus imperialis (Rosaceae) extract in vivo and its potential chemoprevention against cyclophosphamide-induced DNA damage

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

Interactive effects of mechanical ventilation, inhaled nitric oxide and oxidative stress in acute lung injury

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

No Relationship between the Amount of DNA Damage and the Level of hMLH1 and RASSF1A Gene Expression in Bladder Cancer Cells Treated with Cisplatin and Gemcitabine

Tumor response to antineoplastic drugs is not always predictable. This is also true for bladder carcinoma, a highly recurrent neoplasia. Currently, the combination of cisplatin and gemcitabine is well accepted as a standard protocol for treating bladder carcinoma. However, in some cases, this treatment protocol causes harmful side effects. Therefore, we investigated the roles of the genes TP53, RASSF1A (a tumor suppressor gene) and hMLH1 (a gene involved in the mismatch repair pathway) in cell susceptibility to cisplatin/gemcitabine treatment. Two bladder transitional carcinoma cell (TCC) lines, RT4 (wild-type TP53) and 5637 (mutated TP53), were used in this study. First, we evaluated whether the genotoxic potential of cisplatin/gemcitabine was dependent on TP53 status. Then, we evaluated whether the two antineoplastic drugs modulated RASSF1A and hMLH1 expression in the two cell lines. Increased DNA damage was observed in both cell lines after treatment with cisplatin or gemcitabine and with the two drugs simultaneously, as depicted by the comet assay. A lack of RASSF1A expression and hypermethylation of its promoter were observed before and after treatment in both cell lines. On the other hand, hMLH1 downregulation, unrelated to methylation status, was observed in RT4 cells after treatment with cisplatin or with cisplatin and gemcitabine simultaneously (wild-type TP53); in 5637 cells, hMLH1 was upregulated only after treatment with gemcitabine. In conclusion, the three treatment protocols were genotoxic, independent of TP53 status. However, cisplatin was the most effective, causing the highest level of DNA damage in both wild-type and mutated TP53 cells. Gemcitabine was the least genotoxic agent in both cell lines. Furthermore, no relationship was observed between the amount of DNA damage and the level of hMLH1 and RASSF1A expression. Therefore, other alternative pathways might be involved in cisplatin and gemcitabine genotoxicity in these two bladder cancer cell lines.

GENOTOXIC AND MUTAGENIC EFFECTS OF DIFLUBENZURON, AN INSECT GROWTH REGULATOR, ON MICE

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Pre-treatment with glutamine reduces genetic damage due to cancer treatment with cisplatin

Cisplatin is an effective antineoplastic drug. However, it provokes considerable collateral effects, including genotoxic and clastogenic activity. It has been reported that a diet rich in glutamine can help inhibit such collateral effects. We evaluated this activity in 40 Swiss mice, distributed into eight experimental groups: G1 - Control group (PBS 0.1 mL/10g body weight); G2 - cisplatin group (cisplatin 6 mg/kg intraperitoneally); G3, G4, G5 - glutamine groups (glutamine at 150, 300, and 600 mg/kg, respectively; orally); G6, G7, G8 - Pre-treatment groups (glutamine at 150, 300, and 600 mg/kg, respectively; orally and cisplatin 6 mg/kg intraperitonially). For the micronucleus assay, samples of blood were collected (before the first use of the drugs at T0, then 24 (T1) and 48 (T2) hours after the first administration). For the comet assay, blood samples were collected only at T2. The damage reduction percentages for the micronucleus assay were 90.0, 47.3, and 37.3% at T1 and 46.0, 38.6, and 34.7% at T2, for G6, G7, and G8 groups, respectively. For the comet assay, the damage reduction percentages were 113.0, 117.4, and 115.0% for G6, G7, and G8, respectively. We conclude that glutamine is able to prevent genotoxic and clastogenic damages caused by cisplatin.