RESUMO
The economy of the state of Tabasco is based on oil extraction. However, this imposes major effects to the environment and communities. Examples are the Polycyclic Aromatic Hydrocarbons (PAHs) that may be found in the soil, water and sediment of the region. Their volatility makes them available to living beings and results in genotoxic activity. The purpose of this study was to quantify the levels of PAHs in the air at several points in the state, and to analyze their relationship with possible damage to DNA on local inhabitants. Single Cell Gel Electrophoresis Assay (Comet Assay) was applied to peripheral blood lymphocytes of five groups of children between six and 15 years of age. PAH samples were analyzed following US/EPA TO-13-A method. Results indicated the presence in the air of most of the 16 PAHs considered as high priority by EPA, some of which have been reported with carcinogenic activity. Differences (p<0.05) were found between PAHs concentration in the gaseous component and in the particulate component of air samples, with the greatest values for the gaseous component. Greatest PAH concentrations were detected in areas with high oil extraction activities. Children groups from high oil activity areas presented genotoxic damage labeled from moderate to high according to DNA migration from nuclei (Tail Length: 14.2 - 42.14 microm and Tail/Head: 0.97 - 2.83 microm) compared with control group (12.25 and 0.63 microm, respectively). The group with greatest cell damage was located in the area with the greatest oil activity. We conclude that the presence of PAHs in the air may represent a health risk to populations that are chronically exposed to them at high oil activity regions.
Assuntos
Poluentes Atmosféricos/toxicidade , Carcinógenos Ambientais/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Adolescente , Poluentes Atmosféricos/química , Carcinógenos Ambientais/química , Criança , Humanos , México , Testes de Mutagenicidade , Mutagênicos/toxicidadeRESUMO
The mechanisms that control cellular proliferation, as well as those related with programmed cell death or apoptosis, require precise regulation systems to prevent diseases such as cancer. Events related to cellular proliferation as well as those associated with apoptosis involve the regulation of gene expression carried out by three basic genetic expression regulation mechanisms: transcription, splicing of the primary transcript for mature mRNA formation, and RNA translation, a ribosomal machinery-dependent process for protein synthesis. While development of each one of these processes requires energy for recognition and assembly of a number of molecular complexes, it has been reported that an increased expression of several members of these protein complexes promotes apoptosis in distinct cell types. The question of how these factors interact with other proteins in order to incorporate themselves into the different transduction cascades and stimulate the development of programmed cell death, although nowadays actively studied, is still waiting for a clear-cut answer. This review focuses on the interactions established between different families of transcription, elongation, translation and splicing factors associated to the progression of apoptosis.
Assuntos
Apoptose/genética , Expressão Gênica , Fatores de Transcrição E2F/fisiologia , Biossíntese de Proteínas , Splicing de RNA , Fatores de Transcrição STAT/fisiologiaRESUMO
Leukemia-associated antigens such as proteins encoded by MAGE genes might provide tools for immunotherapy of leukemia. Positive and negative results of MAGE-A gene expression in hematological malignancies have been reported. This led us to study MAGE-A gene expression in human leukemias using RT-PCR. Among 115 leukemias from various subtypes, 14/34 (41.17%) AML were positive for one of the three genes analyzed (MAGE-A1 1/32; MAGE-A3 10/32; MAGE-B2 3/12). Expression was also detected in 23/76 (30.26%) B-cell ALL patients (MAGE-A1 2/53; MAGE-A3 20/53; MAGE-B2 1/32). One of these patients expressed both MAGE-A1 (weak signal) and -A3 (strong signal) genes. Other patient with CML were positive for MAGE-B2 (1/5, 20%). MAGE-A3 expression data were corroborated by real time RT-PCR through determination of MAGE-A3 transcript levels. We concluded that the MAGE-A3 gene is expressed at the mRNA level in a proportion of human leukemias.
Assuntos
Antígenos de Neoplasias/genética , Leucemia/genética , Proteínas de Neoplasias/genética , RNA Mensageiro/genética , Transcrição Gênica , Adulto , Antígenos de Neoplasias/sangue , Sequência de Bases , Primers do DNA , Feminino , Amplificação de Genes , Humanos , Leucemia/sangue , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mieloide Aguda/genética , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
P53 mediates several biological processes for preservation of genetic stability such as the induction of cell cycle arrest, DNA repair or apoptosis in response to DNA damage. The antiparasitic drug, 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole (metronidazole, MTZ) is able to increase lymphocyte proliferation inducing at the same time chromosomal aberrations. Trying to understand this unexpected event we used cell lines with different P53 functionality, determining the proliferation capacity and the induction of micronuclei (MN) after the treatment with MTZ or its hydroxy metabolite. Our results show that MTZ increased proliferation in a dose response manner in all P53 functional cell lines without inducing changes on the levels of P53 nor MN. However, MTZ hydroxy metabolite induced a dose response increase of P53 and MN, while cell proliferation was not increased. Several studies have shown that the hydroxy metabolite is more potent than MTZ itself. Only in cell lines that do not have a functional P53, MTZ and its metabolite increased both cell proliferation and MN. MTZ use is increasing and its carcinogenicity has not been discarded. Our data indicate that MTZ hydroxy metabolite is potentially a carcinogen and needs to be further studied.
Assuntos
Anti-Infecciosos/toxicidade , Metronidazol/toxicidade , Micronúcleos com Defeito Cromossômico/efeitos dos fármacos , Proteína Supressora de Tumor p53/fisiologia , Anti-Infecciosos/metabolismo , Divisão Celular/efeitos dos fármacos , Células HeLa , Humanos , Metronidazol/metabolismo , OxirreduçãoRESUMO
BACKGROUND: Albendazole (ABZ) is an antiparasitic drug used for the treatment of several helminthiases. After its oral administration, this compound is metabolized to sulfoxide (SOABZ) and sulfone (SO(2)ABZ), SOABZ being the active metabolite. The antiparasitic activity of ABZ has been associated with its capacity to bind with tubulin, altering microtubule formation. Although some studies indicate that ABZ modified microtubule structure in host cells, data concerning the consequences of this phenomenon in human cells are scant. METHODS: In this study we evaluated the effects of ABZ and its metabolites on cell proliferation, as well as on the frequency of micronucleated cells in cultured human lymphocytes. RESULTS: ABZ and SOABZ arrested cell proliferation in metaphase and increased the frequency of micronuclei in treated lymphocytes. Contrariwise, SO(2)ABZ, the inactive metabolite, did not produce any significant effect. CONCLUSIONS: The formation of micronuclei may ultimately result in aneuploidy induction, an effect that could have severe consequences in humans. However, the doses of ABZ and SOABZ at which these effects were observed are several orders of magnitude higher than those found in the plasma of treated individuals. Because there are other mechanisms by which aneuploidy can be induced at even lower doses than micronuclei, i.e., chromosome nondisjunction, it is necessary to evaluate this effect in exposed individuals.
Assuntos
Albendazol/farmacologia , Anti-Helmínticos/farmacologia , Divisão Celular/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Micronúcleos com Defeito Cromossômico , Adulto , Humanos , Técnicas In Vitro , Ativação Linfocitária/efeitos dos fármacos , Linfócitos/ultraestrutura , MasculinoRESUMO
Neurocysticercosis (NCC) is the most common parasitic infection of the central nervous system. Praziquantel and albendazole are the two cestocide drugs currently used for the treatment of NCC. The present article reviews the studies on the pharmacokinetics of these compounds, both in animals and humans, that have led to more accurate, precise and short treatment schedules for NCC. Toxicological data indicate that both praziquantel and albendazole do not have severe secondary effects in the short term, however, there is still not sufficient information about their long term effects on human health, mainly with respect to albendazole, for which few studies on its effects on human cells are available. These two drugs constitute an effective treatment not only for NCC but also for several helminthiosis. To keep this advantageuos situation, health care professionals should be aware of the necessity of a more rational use of both anthelminthics, since the potentially adverse long term effects could be related to time and dose of exposure as well as to individual susceptibility. In addition, there is always the possibility that the misuse of these compounds could give rise to resistant species, that may represent a significant problem for public health in countries where parasitic diseases are endemic.
Assuntos
Albendazol/uso terapêutico , Anti-Helmínticos/uso terapêutico , Neurocisticercose/tratamento farmacológico , Praziquantel/uso terapêutico , Albendazol/efeitos adversos , Albendazol/farmacocinética , Anti-Helmínticos/efeitos adversos , Anti-Helmínticos/farmacocinética , Humanos , Neurocisticercose/metabolismo , Praziquantel/efeitos adversos , Praziquantel/farmacocinéticaRESUMO
The search for relevant target cells for human monitoring purposes has increased during the last few years. Cells such as sperm, buccal or nasal and gastric epithelium are being used. In this study, we report the use of exfoliated tear duct epithelial cells as a potential material for human biomonitoring studies, since these cells are a target for environmental pollutants. We employed the alkaline single cell gel electrophoresis (SCGE) assay to evaluate for differences in the basal level of DNA damage between young adults from the south (exposed mainly to high levels of ozone) and from the north (exposed principally to hydrocarbons) regions of Mexico City. We found an increase in DNA migration in tear duct epithelial cells from individuals who live in the southern part of the city compared to those living in the northern part. Moreover, young people who live in the southwest part of the city with the highest values of ozone presented the highest values of DNA damage. These results show the feasibility of using exfoliated tear duct epithelial cells in human biomonitoring studies.
Assuntos
Poluentes Atmosféricos/efeitos adversos , Dano ao DNA , Aparelho Lacrimal/efeitos dos fármacos , Adolescente , Adulto , Poluição do Ar/efeitos adversos , Ensaio Cometa , DNA/efeitos dos fármacos , DNA/genética , Oftalmopatias/induzido quimicamente , Oftalmopatias/epidemiologia , Feminino , Humanos , Aparelho Lacrimal/citologia , Aparelho Lacrimal/metabolismo , Masculino , México/epidemiologia , Inquéritos e Questionários , Lágrimas/citologia , Lágrimas/efeitos dos fármacos , Lágrimas/metabolismoRESUMO
Helminths, particularly some Schistosoma species, have been associated with cancer in humans. Neurocysticercosis, produced by cysticerci of the helminth Taenia solium, has been associated with the emergence of brain tumours and haematological malignancies. Local tumours, such as glioblastoma, could be explained by the induction of DNA damage in cells surrounding the cysticercus and chronically exposed to an inflammatory host response. However, systemic effects such as haematological malignancies are not easy to understand. The present work was conducted in Mexico to find out whether DNA damage arises in peripheral lymphocytes in patients with neurocysticercosis. We utilized a highly sensitive technique to analyse chromosomal aberrations, in-situ hybridization with probes against chromosomes 1, 2 and 4, and in addition the blocked-cytokinesis technique was used to determine the formation of micronuclei, a peculiar form of DNA damage. The study was made in lymphocytes from 8 patients before and after the administration of praziquantel, 1 of the 2 drugs used for neurocysticercosis treatment. The frequencies of chromosome aberrations and micronuclei in peripheral blood lymphocytes were higher in the infected patients as compared to those observed both in healthy donors and in the group of patients after praziquantel therapy. Our results suggest that chromosome aberrations induced in peripheral cells during neurocysticercosis could be associated with the development of haematological neoplasias.
Assuntos
Neoplasias Encefálicas/parasitologia , Dano ao DNA , Neoplasias Hematológicas/parasitologia , Linfócitos/ultraestrutura , Neurocisticercose/complicações , Taenia , Adulto , Idoso , Animais , Anti-Helmínticos/uso terapêutico , Neoplasias Encefálicas/genética , Estudos de Casos e Controles , Feminino , Neoplasias Hematológicas/genética , Humanos , Hibridização In Situ , Masculino , Micronúcleos com Defeito Cromossômico/genética , Pessoa de Meia-Idade , Neurocisticercose/tratamento farmacológico , Neurocisticercose/genética , Praziquantel/uso terapêutico , Estatísticas não ParamétricasRESUMO
Industrial development has resulted in an increased release of chemicals and other agents into the environment, resulting in damage to the environment as well as increasing the risk of adverse effects on human health. Environmental toxicology (ET) is the discipline responsible for assessing the risks to human health and the environment from the effects of new chemicals and those already present in the environment. The development of human resources in toxicology is therefore a priority in both Latin America (LA) and the European Union (EU), although LA professionals are more involved in risk evaluation than in risk assessment compared to their EU colleagues. A solid background in general toxicology will enable those interested in environmental issues to tackle local problems. Moreover, the increasing globalization of markets and, therefore, of the necessary regulations, requires harmonisation of postgraduate programmes to ensure that risk assessment and management related to the environment are dealt with uniformly and by highly qualified scientists. The Inaugural Meeting of the ALFA-OMET Toxicology', a 2-year programme supported by the European Commission, offered the opportunity to discuss a number of these issues. The present status of existing ET courses in the EU and LA and the corresponding professional profiles in the two regions were examined, and a harmonized academic curriculum for a postgraduate professional profiles in the two regions were examined, and a harmonized academic curriculum for a postgraduate course in environmental toxicology was developed. Finally, a course programme for toxicology and a specialization in environmental toxicology designed by a panel of experts was discussed, and its relevance as a model for other specialisation programmes was analysed. Exercises such as those performed by ALFA-OMET may be useful not only in promoting discussion for the implementation of national and international professional registers in LA, but also in encouraging the same, ongoing process in the EU.
Assuntos
Poluentes Ambientais/toxicidade , Toxicologia/educação , Europa (Continente) , América LatinaRESUMO
Humans have been in contact with metals almost since the beginning of our existence. In fact, one cannot even think on human evolution without considering the great role played by metals in mankind's development. Metals are common moieties of molecules involved in a wide variety of biological processes, and hence are found in virtually all living organisms. Some metals are essential for human nutrition; others are found as contaminants in foodstuffs. One feature of the normal human diet which is frequently found is the simultaneous presence of both essential and toxic metals. Other factors important in the risk-evaluation analysis of metals are their pharmacokinetics, interactions among them and with other major components of the diet, and, especially, the great differences in the dietary habits of different populations and in the regional distribution of metals. In attempting to understand the role which dietary metals could play in human carcinogenesis, we found that the many factors involved and the lack of specific information made it difficult to reach firm conclusions on the hazards of dietary metals. We hope that this paper will raise the interest of genetic toxicologists in the subject and will consequently facilitate a risk analysis of the carcinogenic potential of dietary metals.