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The effluent discharged by oil refineries is known for its toxicity caused by its inorganic and organic chemicals. The biological effects of the effluent from a treated oil refinery on the bivalve filter feeder of Corbicula fluminea were assessed. DNA damages were assessed through comet assay, the biochemical parameters were measured based on the activity of enzymes such as catalase (CAT) and glutathione S-transferase (GST). Animals were exposed to treatments with effluent for 6, 24 and 96 h. Test animals were allowed to recover from the exposure period for 24, 72 and 144 h. Although animals exposed to the effluent for 96 h presented genotoxicity, they were fully recovered 144 h after the exposure period was over. The CAT activity of animals exposed to the effluent significantly reduced after 24 h of exposure. However, GST activity increased after 96 h of exposure, and its rate remained high after 144 h of recovery; therefore, there was protective GST activity. The damage detected after 96 h of exposure could have been caused by the polycyclic aromatic hydrocarbons (PAH) herein described as DNA intercalating agents. Other compounds such as monoaromatic ethylbenzene, toluene and xylenes (BTEX) were also detected in the assessed effluent. Our study is the first to use the comet assay as genotoxicity cytogenetic biomarker to evaluate the overall recovery ability of bivalve mollusks, mainly of C. fluminea, after their exposure to effluent discharged by oil refineries. Further studies can help better understanding the responses from such exposure and improve knowledge about the persistence of certain disturbances even after contamination is over.

Homeobox genes function as master regulatory transcription factors during development, and their expression is often altered in cancer. The HOX gene family was initially studied intensively to understand how the expression of each gene was involved in forming axial patterns and shaping the body plan during embryogenesis. More recent investigations have discovered that HOX genes can also play an important role in cancer. The literature has shown that the expression of HOX genes may be increased or decreased in different tumors and that these alterations may differ depending on the specific HOX gene involved and the type of cancer being investigated. New studies are also emerging, showing the critical role of some members of the HOX gene family in tumor progression and variation in clinical response. However, there has been limited systematic evaluation of the various contributions of each member of the HOX gene family in the pathways that drive the common phenotypic changes (or “hallmarks”) and that underlie the transformation of normal cells to cancer cells. In this review, we investigate the context of the engagement of HOX gene targets and their downstream pathways in the acquisition of competence of tumor cells to undergo malignant transformation and tumor progression. We also summarize published findings on the involvement of HOX genes in carcinogenesis and use bioinformatics methods to examine how their downstream targets and pathways are involved in each hallmark of the cancer phenotype.

While biallelic mutations in the PALB2 tumor suppressor cause Fanconi anemia subtype FA-N, monoallelic mutations predispose to breast and familial pancreatic cancer. Although hundreds of missense variants in PALB2 have been identified in patients to date, only a few have clear functional and clinical relevance. Herein, we investigate the effects of 44 PALB2 variants of uncertain significance found in breast cancer patients and provide detailed analysis by systematic functional assays. Our comprehensive functional analysis reveals two hotspots for potentially deleterious variations within PALB2, one at each terminus. PALB2 N-terminus variants p.P8L [c.23C>T], p.Y28C [c.83A>G], and p.R37H [c.110G>A] compromised PALB2-mediated homologous recombination. At the C-terminus, PALB2 variants p.L947F [c.2841G>T], p.L947S [c.2840T>C], and most strikingly p.T1030I [c.3089C>T] and p.W1140G [c.3418T>C], stood out with pronounced PARP inhibitor sensitivity and cytoplasmic accumulation in addition to marked defects in recruitment to DNA damage sites, interaction with BRCA2 and homologous recombination. Altogether, our findings show that a combination of functional assays is necessary to assess the impact of germline missense variants on PALB2 function, in order to guide proper classification of their deleteriousness.

Objective Hereditary hearing loss (HL) is the most common sensorineural disorder in humans. Besides mutations in GJB2 and GJB6 genes, pathogenic variants in the SLC26A4 gene have been reported as a cause of hereditary HL due to its role in the physiology of the inner ear. In this research we wanted to investigate the prevalence of mutations in SLC26A4 in Brazilian patients with nonsyndromic prelingual sensorineural HL. We applied the high-resolution melting technique to screen 88 DNA samples from unrelated deaf individuals that were previously screened for GJB2, GJB6 and MT-RNR1 mutations. Results The frequency of mutations in the SLC26A4 gene was 28.4%. Two novel mutations were found: p.Ile254Val and p.Asn382Lys. The mutation c.-66C>G (rs17154282) in the promoter region of SLC26A4, was the most frequent mutation found and was significantly associated with nonsyndromic prelingual sensorineural HL. After mutations in the GJB2, GJB6 and mitochondrial genes, SLC26A4 mutations are considered the next most common cause of hereditary HL in Brazilian as well as in other populations, which corroborates with our data. Furthermore, we suggest the inclusion of the SCL26A4 gene in the investigation of hereditary HL since there was an increase in the frequency of the mutations found, up to 22.7%.

Made available in DSpace on 2018-11-26T15:28:11Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-01-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundacao deAmparo e Pesquisa do Estado do Piaui (FAPEPI) The aim of this study was to evaluate the oxidative parameters of erythrocytes and genotoxicity in leukocytes of patients with breast cancer. Oxidative parameters were detected by spectrophotometry and genotoxic damage by single cell gel electrophoresis. Twenty-eight women with breast cancer were monitored before chemotherapy and after the second and fourth cycles of therapy with cyclophosphamide and doxorubicin. After the fourth cycle, increases (P < 0.05) in the reactive substances to thiobarbituric acid levels, nitrite content, and superoxide dismutase activity and high rates of DNA damage in leukocytes were observed when compared with healthy women group and baseline levels. Similarly, after the second cycle, the same parameters were increased (P < 0.05) when compared with baseline levels. Increase in catalase activity was detected only after the fourth cycle and reduced glutathione levels and glutathione peroxidase activity were decreased in all cycles when compared with healthy women, as well as after the second and fourth chemotherapy cycles compared to baseline (P < 0.05). Patients with breast cancer presented an indicative of oxidative stress before, during, and after chemotherapy, as well as increased genotoxic damage in all stages of treatment, demonstrating the clinical applicability of this investigation. Univ Fed Piaui, Lab Genet Tox, Postgrad Program Pharmaceut Sci, BR-64049550 Teresina, PI, Brazil State Univ Sao Paulo, Postgrad Program Genet, BR-14049900 Ribeirao Preto, SP, Brazil Univ Fed Piaui, Dept Physiol & Biophys, Postgrad Program Pharmaceut Sci, Lab Expt Cancerol, BR-64049550 Teresina, PI, Brazil Univ Alabama, Dept Chem, Huntsville, AL 35899 USA Univ Fed Piaui, Lab Res Expt Neurochem, Postgrad Program Pharmaceut Sci, BR-64049550 Teresina, PI, Brazil State Univ Sao Paulo, Postgrad Program Genet, BR-14049900 Ribeirao Preto, SP, Brazil