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1.
Biol Res ; 47: 62, 2014 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-25723567

RESUMO

BACKGROUND: The mortality of lung cancer (LC), increases each year in the world, in spite of any advances, in development of new drugs to advance stages of LC. The high incidence of LC has been associated with smoking habit, genetic diversity and environmental pollution. Antofagasta region has been reported to have the highest LC mortality rate in Chile and its inhabitants were exposed to arsenic in their drinking water in concentrations as high as 870 µg/L. Non-invasive techniques such as biomarkers (Automatic Quantitative Cytometry: AQC and DR70) and Auto Fluorescence Bronchoscopy (AFB) might be potentially useful as a supplementary diagnostic approach and early detection. Early detection is one of the most important factors to intervene and prevent cancer progression in LC. This is a work of an ongoing prospective bimodality cancer surveillance study in high risk LC volunteers. Enrolment was done in subjects from Antofagasta and Metropolitan regions. In addition, we enrolled subjects who were suspected of having lung cancer. AQC, DR70 and AFB were used as tools in the detection of pre-neoplastic (PNL) and neoplastic lesions (NL). RESULTS: Half of the samples, classified as suspicious by AFB, were confirmed as metaplasia or dysplasia by histopathology. For LC, DR70 showed a higher sensitivity (95.8%) and specificity (91.9%) than AQC. However, for PNL AQC showed a higher sensitivity (91.9%) than DR70 (27.3%), although both with low PPV values. As a pre screener, both biomarkers might be employed as complementary tools to detect LC, especially as serially combined tests, with a sensitivity of 60% and a PPV of 65.2%. Additionally, the use of parallel combined tests might support the detection of PNL (sensitivity 91.2%; PPV 49.1%). CONCLUSION: This work adds information on cellular and molecular biomarkers to complement imaging techniques for early detection of LC in Latin America that might contribute to formulate policies concerning screening of LC. Supported by INNOVA-CORFO, Chile.


Assuntos
Adenocarcinoma/patologia , Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/patologia , Lesões Pré-Cancerosas/patologia , Adenocarcinoma/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Broncoscopia/métodos , Carcinoma/epidemiologia , Carcinoma/patologia , Chile/epidemiologia , Intervalos de Confiança , Método Duplo-Cego , Feminino , Humanos , Citometria por Imagem/normas , Neoplasias Pulmonares/epidemiologia , Masculino , Metaplasia/diagnóstico , Pessoa de Meia-Idade , Imagem Óptica/normas , Valor Preditivo dos Testes , Prevalência , Estudos Prospectivos , Curva ROC , Medição de Risco , Vigilância de Evento Sentinela , Carcinoma de Pequenas Células do Pulmão/epidemiologia , Carcinoma de Pequenas Células do Pulmão/patologia , Escarro/citologia
2.
Biol. Res ; 47: 1-9, 2014. graf, tab
Artigo em Inglês | LILACS | ID: biblio-950758

RESUMO

BACKGROUND: The mortality of lung cancer (LC), increases each year in the world, in spite of any advances, in development of new drugs to advance stages of LC. The high incidence of LC has been associated with smoking habit, genetic diversity and environmental pollution. Antofagasta region has been reported to have the highest LC mortality rate in Chile and its inhabitants were exposed to arsenic in their drinking water in concentrations as high as 870 µg/L. Non-invasive techniques such as biomarkers (Automatic Quantitative Cytometry: AQC and DR70) and Auto Fluorescence Bronchoscopy (AFB) might be potentially useful as a supplementary diagnostic approach and early detection. Early detection is one of the most important factors to intervene and prevent cancer progression in LC. This is a work of an ongoing prospective bimodality cancer surveillance study in high risk LC volunteers. Enrolment was done in subjects from Antofagasta and Metropolitan regions. In addition, we enrolled subjects who were suspected of having lung cancer. AQC, DR70 and AFB were used as tools in the detection of pre-neoplastic (PNL) and neoplastic lesions (NL). RESULTS: Half of the samples, classified as suspicious by AFB, were confirmed as metaplasia or dysplasia by histopathology. For LC, DR70 showed a higher sensitivity (95.8%) and specificity (91.9%) than AQC. However, for PNL AQC showed a higher sensitivity (91.9%) than DR70 (27.3%), although both with low PPV values. As a pre screener, both biomarkers might be employed as complementary tools to detect LC, especially as serially combined tests, with a sensitivity of 60% and a PPV of 65.2%. Additionally, the use of parallel combined tests might support the detection of PNL (sensitivity 91.2%; PPV 49.1%). CONCLUSION: This work adds information on cellular and molecular biomarkers to complement imaging techniques for early detection of LC in Latin America that might contribute to formulate policies concerning screening of LC. Supported by INNOVA-CORFO, Chile.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Lesões Pré-Cancerosas/patologia , Adenocarcinoma/patologia , Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/patologia , Escarro/citologia , Broncoscopia/métodos , Carcinoma/patologia , Carcinoma/epidemiologia , Adenocarcinoma/epidemiologia , Intervalos de Confiança , Chile/epidemiologia , Método Duplo-Cego , Prevalência , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Vigilância de Evento Sentinela , Medição de Risco , Citometria por Imagem/normas , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/epidemiologia , Imagem Óptica/normas , Neoplasias Pulmonares/epidemiologia , Metaplasia/diagnóstico
3.
J Thorac Oncol ; 8(11): 1451-5, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24128716

RESUMO

INTRODUCTION: Arsenic exposure is a significant cause of lung cancer in North America and worldwide. Arsenic-related tumors are structurally indistinguishable from those induced by other carcinogens. Because carcinogens, like tobacco, induce distinctive mutational signatures, we sought to characterize the mutational signature of an arsenic-related lung tumor from a never smoker with the use of whole-genome sequencing. METHODS: Tumor and lung tissues were obtained from a never smoker with lung squamous cell carcinoma (LUSC), without familiar history of lung cancer and chronically exposed to high levels of arsenic-contaminated drinking water. The Illumina HiSeq-2000 platform was used to sequence each genome at approximately 30-fold haploid coverage. The mutational signature was compared with those observed in previously characterized lung tumors. RESULTS: The arsenic-related tumor exhibited alterations common in LUSC, such as the increased number of copies at 3q26 (SOX2 locus). However, the arsenic-related genome not only harbored a lower number of point mutations, but also had a remarkably high fraction of T>G/A>C mutations and low fraction of C>A/G>T transversions, which is uncharacteristic of LUSCs. Furthermore, at the gene level, we identified a rare G>C mutation in TP53, which is uncommon in lung tumors in general (<0.2%) but has been observed in other arsenic-related malignancies. CONCLUSIONS: We generated the first whole-genome sequence of an LUSC from a never-smoker patient chronically exposed to arsenic, and identified a distinct mutational spectrum associated with arsenic exposure, providing novel evidence supporting the hypothesis that arsenic-induced lung tumors arise through molecular mechanisms that differ from those of the common lung cancer.


Assuntos
Intoxicação por Arsênico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/genética , Genoma Humano , Mutação Puntual/genética , Análise de Sequência de DNA , Proteína Supressora de Tumor p53/genética , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia
4.
Mol Biol Int ; 2011: 718974, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22091411

RESUMO

Chronic exposure to arsenic in drinking water poses a major global health concern. Populations exposed to high concentrations of arsenic-contaminated drinking water suffer serious health consequences, including alarming cancer incidence and death rates. Arsenic is biotransformed through sequential addition of methyl groups, acquired from s-adenosylmethionine (SAM). Metabolism of arsenic generates a variety of genotoxic and cytotoxic species, damaging DNA directly and indirectly, through the generation of reactive oxidative species and induction of DNA adducts, strand breaks and cross links, and inhibition of the DNA repair process itself. Since SAM is the methyl group donor used by DNA methyltransferases to maintain normal epigenetic patterns in all human cells, arsenic is also postulated to affect maintenance of normal DNA methylation patterns, chromatin structure, and genomic stability. The biological processes underlying the cancer promoting factors of arsenic metabolism, related to DNA damage and repair, will be discussed here.

5.
Electron. j. biotechnol ; 10(2): 169-177, Apr. 15, 2007. ilus, graf
Artigo em Inglês | LILACS | ID: lil-499184

RESUMO

The benefits of today's biotechnology products are not evident to consumers. The public will accept biotechnology only when individuals decide for themselves that biotec products will contribute to their personal well-being. To make such a decision, people will need greater awareness and understanding of how biotechnology will affect the environment, human health, local and national economies, and the well-being of society. A low level of awareness and understanding about biotechnology is characteristic of Latin America and the Caribbean countries, as elsewhere, efforts to remedy poor public perception often seem inadequate and do not reflect a well-designed strategy. In order to improve the understanding of the biotechnology and their human applications, a strategic plan for public communications is required. Specific objectives for this initiative may include: (1) to make evident to decision makers that modern biotechnology can be an effective tool for increasing agricultural productivity, and thereby economic growth, without imposing unacceptable risk to the environment or human and animal health; (2) to enable members of the public to make informed decisions about appropriate uses of biotechnology by providing accurate information about benefits, risks and impacts; or (3) to incorporate modern biotechnology into science curricula for secondary schools, university and college students, and agriculture extension officers. A variety of specialized expertise, including communication specialists, technical writers, graphic artists and illustrators to design information materials and conduct training is needed to implement this. Ideally, members bring expertise in biotechnology and biosafety, public communications and project management. The plan will need to identify scientists and technical experts who can provide expertise in science writing for general audiences...


Assuntos
Humanos , Biotecnologia , Alimentos Geneticamente Modificados , Opinião Pública , Percepção Social , Conhecimentos, Atitudes e Prática em Saúde
6.
J Occup Environ Med ; 45(9): 984-92, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-14506341

RESUMO

This work studied the mutagenic potential and polycyclic aromatic hydrocarbon (PAH) levels onto PM10 collected in diesel revision plants, in an urban area as well as in a rural area in Santiago, Chile. The PM10 average levels in diesel emission plants during working hours (there is no occupational PM10 Chilean standard) were significantly higher than the atmospheric Chilean PM10 standard and highly mutagenic and with high PAHs levels. Additionally, we evaluated the contribution of CYP1A1 and GSTM1 polymorphisms on 1-OH-pyrene urinary levels. The diesel-exposed workers carrying the CYP1A1*2A allele showed significantly higher 1-OH-P levels than the subjects from the rural area with the same genotype. The higher levels of 1-OH-P were found in individuals carrying the combined CYP1A1*2A and GSTM1 null genotype. This kind of information might be relevant to establish prevention, protection, and mitigation actions to protect public health.


Assuntos
Poluentes Ocupacionais do Ar/análise , Monitoramento Ambiental , Mutagênicos/efeitos adversos , Exposição Ocupacional/análise , Saúde Ocupacional , Hidrocarbonetos Policíclicos Aromáticos/análise , Emissões de Veículos/análise , Adulto , Poluentes Ocupacionais do Ar/efeitos adversos , Chile , Feminino , Humanos , Masculino , Metalurgia , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Tamanho da Partícula , Hidrocarbonetos Policíclicos Aromáticos/efeitos adversos , Probabilidade , Medição de Risco , Emissões de Veículos/efeitos adversos
7.
Santiago; Organización Panamericana de la Salud; ago. 1997. 239 p. ilus.(OPS. Serie HCT/AIEPI, 7).
Monografia em Espanhol | PAHO | ID: pah-24376
8.
Santiago; Organización Panamericana de la Salud; ago. 1997. 239 p. ilus.(OPS. Serie HCT/AIEPI, 7).
Monografia em Espanhol | LILACS | ID: lil-377024
9.
Ciênc. cult. (Säo Paulo) ; 48(1/2): 51-4, Jan.-Apr. 1996. tab
Artigo em Inglês | LILACS | ID: lil-191242

RESUMO

This study describes the changes induced by organic extracts from airborne particuiate matter in some enzymes related to the antioxidant defense system as well as in peroxisomal acyl CoA oxidase activity in rat liver. After 48 h of i.p. injection (40 mg/kg b.wt.) the hepatic GSH content decreased by about 30 per cent, which was accompanied by a parallel increase in glutathione-S-transferase activity. In contrast the activity of glutathione peroxidase was significantly decreased (p < 0.05).Peroxisomal acyl CoA-oxidase was enhanced by about 40 per cent with a parallel increase of liver catalase (27 per cent), the peroxisomal H2O2-destroying enzyme. With the only exception hepatic lipid peroxidation, that remains unchanged, all the effects showed a dose-dependent response with respect to the content of polycyclic aromatic hydrocarbons in the organic airborne extracts. However, the content of other chemical pollutants such as plasticizers, pestcides and other organic compounds must be taken into account. These results suggest that organic extracts from Santiago airborne particles might induce a prooxidant state. According to this view the increase in GSTs and catalase activity may be considered as a protective response against the damage induced by airborne pollutants.


Assuntos
Animais , Ratos , Poluentes Atmosféricos/efeitos adversos , Antioxidantes/metabolismo , Enzimas/metabolismo , Fígado/enzimologia , População Urbana , Acil Coenzima A/metabolismo , Catalase/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa/metabolismo
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