Análise da mutagenecidade urinária e susceptibilidade genética no monitoramento de indivíduos expostos a solventes orgânicos
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Data
2005-10-04
Autores
Varella, Soraya Duarte [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
A exposição ocupacional a solventes orgânicos é um sério problema para milhares de trabalhadores. A literatura demonstra a ocorrência de um elevado risco de danos no material genético desses indivíduos, no entanto, os efeitos da mistura dos solventes orgânicos não são bem conhecidos. As diferenças genéticas (polimorfismos enzimáticos) também têm um importante papel na capacidade de ativação e de detoxificação de xenobióticos, incluindo os solventes orgânicos. As mutações causadas por agentes ambientais associadas aos diferentes genótipos, são fatores relacionados ao desenvolvimento de neoplasias e outras doenças degenerativas. O ensaio de mutagenicidade urinária indica a ocorrência de possíveis lesões préclínicas enquanto que a determinação dos polimorfismos enzimáticos mostra um perfil genético de risco. Assim, os profissionais da saúde envolvidos com a qualidade de vida do trabalhador, podem ter subsídios para o controle da exposição ocupacional e conseqüentemente evitar o aparecimento de doença (lesão clínica), principalmente o câncer. O trabalho diário num laboratório de pesquisa onde são utilizados vários tipos de solventes é igualmente preocupante. Diante disso, este estudo teve os seguintes objetivos: caracterizar a atividade mutagênica na urina de 30 indivíduos ocupacionalmente expostos a solventes orgânicos e indivíduos sem essa exposição (controles); identificar o polimorfismo constitucional desses indivíduos para os genes GSTM1, GSTT1 e CYP2E1 ; e tentar correlacionar a influência desses genótipos com a atividade mutagênica urinária. A coleta da urina foi realizada em frascos de polietileno durante o dia de trabalho, até a obtenção de aproximadamente 1000mL. Para a concentração e extração dos compostos presentes na urina foi usada a resina XAD-2 e o solvente acetona. Diferentes concentrações...
The occupational exposure to organic solvents is a serious problem to millions of workers. The reports shows a high risk of genetic damage on these workers. However, the effects of mixtures of solvents are not well known. The genetic differences (enzimatic polymorphisms) are very important for the capacity of activating and detoxifying carcinogens, such as organic solvents. Mutations caused by environmental agents associated with the different genotypes are related to cancer development and other degenerative diseases. The urinary mutagenicity assay shows pre-clinical damages while the enzimatic polymorphisms show a genetic risk profile. In this way, the health professionals can have subsity to occupational exposure control in order to avoid disease development (clinical damage), cancer especially. The work in a research laboratory that uses several types of solvents is equaly preocupating. In this way, in this study the genotyping approach was used to study the influence of the metabolic polymorphisms CYP2E1, GSTM1 and GSTT1 on urinary mutagenicity, detected with Salmonella/microsome assay, in 30 subjects exposed to solvents, and 30 subjects without occupational exposure (controls). Urine samples were collected in polyethylene containers at the end of the work shift. For the concentration and extraction of urine samples was used the XAD-2 resin and acetone as eluting agent. Different doses of extract (1.5; 3.0; 6.0 and 12.0 mL equivalents per plate) were tested on Salmonella typhimurium strains TA100 and YG1024, with and without metabolic activation. Genomic DNA was extracted from blood and the GSTM1, GSTT1 and CYP2E1-PstI genotypes were deternined using a PCR method. The mutagenic activity of urine samples from exposed workers shows a significant difference (p£ 0.05) when compared to those in the control group in the Salmonella typhimurium YG1024 with S9 mix... (Complete abstract, click electronic access below)
The occupational exposure to organic solvents is a serious problem to millions of workers. The reports shows a high risk of genetic damage on these workers. However, the effects of mixtures of solvents are not well known. The genetic differences (enzimatic polymorphisms) are very important for the capacity of activating and detoxifying carcinogens, such as organic solvents. Mutations caused by environmental agents associated with the different genotypes are related to cancer development and other degenerative diseases. The urinary mutagenicity assay shows pre-clinical damages while the enzimatic polymorphisms show a genetic risk profile. In this way, the health professionals can have subsity to occupational exposure control in order to avoid disease development (clinical damage), cancer especially. The work in a research laboratory that uses several types of solvents is equaly preocupating. In this way, in this study the genotyping approach was used to study the influence of the metabolic polymorphisms CYP2E1, GSTM1 and GSTT1 on urinary mutagenicity, detected with Salmonella/microsome assay, in 30 subjects exposed to solvents, and 30 subjects without occupational exposure (controls). Urine samples were collected in polyethylene containers at the end of the work shift. For the concentration and extraction of urine samples was used the XAD-2 resin and acetone as eluting agent. Different doses of extract (1.5; 3.0; 6.0 and 12.0 mL equivalents per plate) were tested on Salmonella typhimurium strains TA100 and YG1024, with and without metabolic activation. Genomic DNA was extracted from blood and the GSTM1, GSTT1 and CYP2E1-PstI genotypes were deternined using a PCR method. The mutagenic activity of urine samples from exposed workers shows a significant difference (p£ 0.05) when compared to those in the control group in the Salmonella typhimurium YG1024 with S9 mix... (Complete abstract, click electronic access below)
Descrição
Palavras-chave
Mutagenicidade urinária, Polimorfismo enzimático, Exposição ocupacional, Teste de Arnês, Urinary mutagenicy, Enzimatic polymorphism, Occupational exposure, Ames test
Como citar
VARELLA, Soraya Duarte. Análise da mutagenecidade urinária e susceptibilidade genética no monitoramento de indivíduos expostos a solventes orgânicos. 2005. 98 f. Tese (doutorado) - Universidade Estadual Paulista, Faculdade de Ciências Farmacêuticas, 2005.