28 research outputs found
Genotoxic effects in occupational exposure to formaldehyde: A study in anatomy and pathology laboratories and formaldehyde-resins production
ABSTRACT – Background: According to the Report on Carcinogens, formaldehyde ranks 25th in the overall U.S. chemical production, with more than 5 million tons produced each year. Given its economic importance and widespread use, many people are exposed to formaldehyde environmentally and/or occupationally. Presently, the International Agency for Research on Cancer classifies formaldehyde as carcinogenic to humans (Group 1), based on sufficient evidence in humans and in experimental animals. Manyfold in vitro studies clearly indicated that formaldehyde can induce genotoxic effects in proliferating cultured mammalian cells. Furthermore, some in vivo studies have found changes in epithelial cells and in peripheral blood lymphocytes related to formaldehyde exposure. Methods: A study was carried out in Portugal, using 80 workers occupationally exposed to formaldehyde vapours: 30 workers from formaldehyde and formaldehyde-based resins production factory and 50 from 10 pathology and anatomy laboratories. A control group of 85 non-exposed subjects was considered. Exposure assessment was performed by applying simultaneously two techniques of air monitoring: NIOSH Method 2541 and Photo Ionization Detection equipment with simultaneously video recording. Evaluation of genotoxic effects was performed by application of micronucleus test in exfoliated epithelial cells from buccal mucosa and peripheral blood lymphocytes. Results: Time-weighted average concentrations not exceeded the reference value (0.75 ppm) in the two occupational settings studied. Ceiling concentrations, on the other hand, were higher than reference value (0.3 ppm) in both. The frequency of micronucleus in peripheral blood lymphocytes and in epithelial cells was significantly higher in both exposed groups than in the control group (p < 0.001). Moreover, the frequency of micronucleus in peripheral blood lymphocytes was significantly higher in the laboratories group than in the factory workers (p < 0.05). A moderate positive correlation was found between duration of occupational exposure to formaldehyde (years of exposure) and micronucleus frequency in peripheral blood lymphocytes (r = 0.401; p < 0.001) and in epithelial cells (r = 0.209; p < 0.01). Conclusions: The population studied is exposed to high peak concentrations of formaldehyde with a long-term exposure. These two aspects, cumulatively, can be the cause of the observed genotoxic endpoint effects. The association of these cytogenetic effects with formaldehyde exposure gives important information to risk assessment process and may also be used to assess health risks for exposed worke
Identification of four new susceptibility loci for testicular germ cell tumour
Genome wide association studies (GWAS) have identified multiple risk loci for testicular germ cell tumour (TGCT), revealing a polygenic model of disease susceptibility strongly influenced by common variation. To identify further SNPs associated with TGCT we conducted a multistage GWAS with combined dataset of >25,000 individuals (6,059 cases and 19,094 controls). We identified new risk loci for TGCT at 3q23 (rs11705932, TFDP2, P = 1.5 x 10-9), 11q14.1 (rs7107174, GAB2, P = 9.7 x 10-11), 16p13.13 (rs4561483, GSPT1, P = 1.6 x 10-8) and 16q24.2 (rs55637647, ZFPM1, P = 3.4 x 10-9). We additionally present detailed functional analysis of these loci, identifying a strong relationship between rs4561483 risk genotype and increased GSPT1 expression in TGCT patient samples. These findings provide additional support for a polygenic model of TGCT risk and further insight into the biologic basis of disease development
BCL6 degradation caused by the interaction with the C-terminus of pro-HB-EGF induces cyclin D2 expression in gastric cancers
BCL6 is a transcriptional repressor that has important functions in lymphocyte differentiation and lymphomagenesis, but there have been no reports of BCL6 expression in gastric cancers. In the present study, we investigated the BCL6 function in gastric cancers. Treatment with TPA resulted in BCL6 degradation and cyclin D2 upregulation. This phenomenon was inhibited by the suppression of the nuclear translocation of HB-EGF-CTF (C-terminal fragment of pro-HB-EGF). The HB-EGF-CTF nuclear translocation leads to the interaction of BCL6 with HB-EGF-CTF and the nuclear export of BCL6, and after that BCL6 degradation was mediated by ubiquitin/proteasome pathway. Real-time RT–PCR and siRNA targeting BCL6 revealed that BCL6 suppresses cyclin D2 expression. Our data indicate that BCL6 interacts with nuclear-translocated HB-EGF-CTF and that the nuclear export and degradation of BCL6 induces cyclin D2 upregulation. We performed immunohistochemical analyses of BCL6, HB-EGF and cyclin D2 in human gastric cancers. The inverse correlation between BCL6 and cyclin D2 was also found in HB-EGF-positive human gastric cancers. BCL6 degradation caused by the HB-EGF-CTF also might induce cyclin D2 expression in human gastric cancers. Inhibition of HB-EGF-CTF nuclear translocation and maintenance of BCL6 function are important for the regulation of gastric cancer progression
Identificação molecular de Aspergillus fumigatus em amostras de ar interior
Os bioaerossóis são essencialmente compostos por partÃculas
fúngicas, bactéricas e esporos de plantas, sendo os fungos
responsáveis pela produção de compostos orgânicos voláteis
e micotoxinas. A sua presença no ar interior está associada a
manifestações alérgicas, tóxicas e infecciosas. Tais respostas
dependem não só da susceptibilidade do indivÃduo como das
espécies e concentrações de fungos presentes. Os trabalhadores
de aviários e suiniculturas são profissionais com elevada
exposição a estes agentes, pelo que têm maior risco de desenvolvimento
de patologias associadas.
Com este estudo pretende‑se
desenvolver um método rápido
e de elevada especificidade e sensibilidade que permita identificar
as espécies de fungos clinicamente relevantes em contexto
de saúde ocupacional.
Foi utilizado o Coriolis Air sampler para proceder à recolha de
amostras de ar interior (300 Lmin‑1)
em seis instalações de criação
de aves e suÃnos. O DNA fúngico foi isolado das amostras
utilizando o kit Zymo ZR Fungal/Bacterial DNA e a sua presença
foi confirmada utilizando primers universais para fungos.
A presença de Aspergillus fumigatus foi pesquisada por PCR
em Tempo Real utilizando sondas Taqman e primers especÃficos.
Os resultados obtidos foram comparados com os determinados
por métodos convencionais de cultura.
Foram obtidas 25 amostras de 300L de ar em seis instalações.
Os resultados obtidos confirmam a presença de A. fumigatus
em todas as amostras de ar em que esta espécie foi identificada
através de culturas (3/25). Adicionalmente, foi também
detectada em amostras de ar correspondendo a instalações
em que, através de culturas, esta espécie não foi identificada
no ar interior (6/25).
Os resultados preliminares sugerem maior sensibilidade dos
métodos moleculares relativamente aos métodos convencionais
de cultura. Futuramente, pretende‑se
aplicar a mesma
metodologia para identificação de um maior número de espécies
e proceder à sua quantificação.Abstract publicado em: SAÚDE & TECNOLOGIA . 2011 | Suplemento | P. 74 . ISSN: 1646-970
Accessing indoor fungal contamination by Aspergillus fumigatus complex using conventional and molecular methods in portuguese poultries
Epidemiological studies showed increased prevalence of respiratory symptoms and adverse changes in pulmonary function parameters in poultry workers, corroborating the increased exposure to risk factors, such as fungal load and their metabolites. This study aimed to determine the occupational exposure threat due to fungal contamination caused by the toxigenic isolates belonging to the complex of the species of Aspergillus flavus and also isolates from Aspergillus fumigatus species complex. The study was carried out in seven Portuguese poultries, using cultural and molecular methodologies. For conventional/cultural methods, air, surfaces, and litter samples were collected by impaction method using the Millipore Air Sampler. For the molecular analysis, air samples were collected by impinger method using the Coriolis μ air sampler. After DNA extraction, samples were analyzed by real-time PCR using specific primers and probes for toxigenic strains of the Aspergillus flavus complex and for detection of isolates from Aspergillus fumigatus complex. Through conventional methods, and among the Aspergillus genus, different prevalences were detected regarding the presence of Aspergillus flavus and Aspergillus fumigatus species complexes, namely: 74.5 versus 1.0 % in the air samples, 24.0 versus 16.0 % in the surfaces, 0 versus 32.6 % in new litter, and 9.9 versus 15.9 % in used litter. Through molecular biology, we were able to detect the presence of aflatoxigenic strains in pavilions in which Aspergillus flavus did not grow in culture. Aspergillus fumigatus was only found in one indoor air sample by conventional methods. Using molecular methodologies, however, Aspergillus fumigatus complex was detected in seven indoor samples from three different poultry units. The characterization of fungal contamination caused by Aspergillus flavus and Aspergillus fumigatus raises the concern of occupational threat not only due to the detected fungal load but also because of the toxigenic potential of these species
Modulation of translation factor's gene expression by histone deacetylase inhibitors in breast cancer cells
The histone deacetylase inhibitors sodium butyrate (NaBu) and trichostatin A (TSA) exhibit anti-proliferative activity by causing cell cycle arrest and apoptosis. The mechanisms by which NaBu and TSA cause apoptosis and cell cycle arrest are not yet completely clarified, although these agents are known to modulate the expression of several genes including cell-cycle- and apoptosis-related genes. The enzymes involved in the process of translation have important roles in controlling cell growth and apoptosis, and several of these translation factors have been described as having a causal role in the development of cancer. The expression patterns of the translation mechanism, namely of the elongation factors eEF1A1 and eEF1A2, and of the termination factors eRF1 and eRF3, were studied in the breast cancer cell line MCF-7 by real-time quantitative reverse transcription-polymerase chain reaction after a 24-h treatment with NaBu and TSA. NaBu induced inhibition of translation factors' transcription, whereas TSA caused an increase in mRNA levels. Thus, these two agents may modulate the expression of translation factors through different pathways. We propose that the inhibition cau- sed by NaBu may, in part, be responsible for the cell cycle arrest and apoptosis induced by this agent in MCF-7 cells
An island within an island: genetic differentiation of Anopheles gambiae in São Tomé, West Africa, and its relevance to malaria vector control.
Islands are choice settings for experimental studies of vector
control strategies based on transgenic insects. Before
considering this approach, knowledge of the population
structure of the vector is essential. Genetic variation at 12
microsatellite loci was therefore studied in samples of the
malaria vector Anopheles gambiae s.s., collected from six
localities of Sa˜o Tome´ island (West Africa). The objectives
were (i) to assess the demographic stability and effective
population size of A. gambiae from these sites, (ii) to
determine population differentiation and (iii) to relate the
observed patterns of population structure with geographic,
ecological and historical aspects of the vector on the island.
Significant population differentiation, revealed by FST and
RST statistics, was found between the southernmost site,
Porto Alegre, and northern localities. The observed patterns
of population substructure are probably a result of restrictions
to gene flow in the less inhabited, more densely forested and
mountainous south. In all localities surveyed, A. gambiae
appeared to be experiencing a demographic expansion,
consistent with a relatively recent (ca. 500 years) founder
effect. The results are discussed with respect to current and
future prospects of malaria vector control.
Heredity (2003) 91, 407–414. doi:10.1038/sj.hdy.680034