Chromosome aberrations as a predictor of clinical outcome for smoking associated lung cancer

The ability to identify individuals at greatest risk of developing lung cancer can significantly enhance the efficacy of intervention modalities. One strategy for identifying these individuals is through biomarkers that reflect the severity of their cancer. In the present study, we evaluated 22 lung cancer patients and 35 controls to determine whether the frequency of chromosome aberrations was significantly associated with specific clinical variables such as the histological type, grade and stage of the turners. Chromosome aberrations (expressed as total breaks) were investigated on chromosome 1 in interphase nuclei obtained from blood Lymphocytes of the study participants using the fluorescence in situ hybridization (FISH) chromosome aberration assay. Our results indicate a significant linear increase (P = 0.01) in the level of breaks with respect to the grade of the carcinoma. The poorly differentiated tumors had a significantly higher level of chromosome breaks mean +/- SD (1.7 +/- 0.46) as compared to the well differentiated tumors (0.98 +/- 0,23, P < 0,05). These results indicate that chromosome aberrations, as determined by the FISH assay, can be used as a biomarker for identifying individuals with aggressive types of lung cancer and potentially, as a predictor for prognostic outcome of the disease. (C) 2000 Elsevier B.V. Ireland Ltd. All rights reserved

Otimização e validação de uma metodologia analítica para determinação de 1-hidroxipireno em urina de cortadores de cana-de-açúcar

Este trabalho teve como objetivo otimizar e validar uma metodologia analítica para determinação de 1-hidróxipireno em urina de trabalhadores envolvidos na colheita da cana-de-açúcar. O método utilizado para determinação de 1-hidroxipireno em urina humana utilizado consiste na hidrólise enzimática, extração e clean-up por extração em fase sólida (SPE) e quantificação por cromatografia líquida de alta eficiência com detector de fluorescência (CLAE/Flu). Quatro tipos de cartuchos foram testados para verificação da porcentagem de recuperação. Urina de cortadores de cana-de-açúcar (não-fumantes e de ambos os sexos) foram coletadas no período da safra (n=39) e entressafra (n=34) da cana-de-açúcar. Os melhores resultados de recuperação foram atribuídos aos cartuchos C18. Os mesmos apresentaram recuperação entre 79% e 108%, com coeficiente de variação entre 5% e 10%. O limite de quantificação do método foi de 74 ng de 1-hidroxipireno por litro de urina. A metodologia otimizada e validada foi utilizada para determinação de amostras reais. Os resultados encontrados na urina dos trabalhadores no período da safra variaram de 0,026 a 2,3 μmol de 1-hidroxipireno por mol de creatinina. No período da entressafra os resultados variaram de 0,0023 a 0,38 μmol de 1-hidroxipireno por mol de creatinina. A metodologia validada mostrou-se adequada para determinação de 1-hidroxipireno em urina humana. Os dados obtidos permitem concluir que há forte correlação entre excreção de 1-hidroxipireno e os períodos de safra e entressafra da cana de açúcar.This study aimed to optimize and validate an analytical methodology for determination of 1-hydroxypyrene in urine of workers involved in harvesting sugar cane. The method used for determining 1-hydroxypyrene in human urine is the enzymatic hydrolysis, extraction and clean-up by solid phase extraction (SPE) and quantified by high performance liquid chromatography with fluorescence detection (HPLC / Flu). Four types of cartridges were tested to verify the percentage of recovery. Urine of sugar-cane workers (non-smokers and of both sexes) were collected during the harvest (n = 39) and non-harvest season (n = 34) of cane sugar. The best recovery results were attributed to the C18 cartridges. They presented recovery between 79% and 108%, with a coefficient of variation between 5% and 10%. The limit of quantification was 74 ng of 1-hydroxypyrene per liter of urine. The optimized and validated methodology was used for determination of real samples. The results found in the urine of workers at harvest period ranged from 0.026 to 2.3 μmol of 1-hydroxypyrene per mol creatinine. During the non-harvesting season the results ranged from 0.0023 to 0.38 μmol of 1-hydroxypyrene per mol creatinine. The validated methodology proved suitable for determination of 1-hydroxypyrene in human urine. The data indicate that there is strong correlation between excretion of 1-hydroxypyrene and the periods during and between harvests of sugar cane.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP