Valoración de la exposición a plaguicidas en cultivos extensivos de Argentina y su potencial impacto sobre la salud / Pesticide Exposure Assessment in Argentinian Extensive Crops and its Potential Health Impact

INTRODUCCIÓN: Los plaguicidas configuran un aspecto central de las prácticas agrícolas. OBJETIVOS: Describir la distribución espacial de la exposición a plaguicidas en Argentina y su asociación con indicadores de carga de cáncer, construir índices de exposición global y validar índices de exposición individual con biomarcadores de efecto en sujetos laboralmente expuestos. MÉTODOS: Se construyeron dos índices globales (de exposición a plaguicidas [IEP] y de impacto ambiental total [IIAT]), se estudiaron sus distribuciones espaciales y mediante un estudio ecológico a nivel nacional se estimó la asociación con las tasas de mortalidad de cáncer total, mama y próstata, usando los departamentos como nivel de desagregación (n=564). Dos índices de exposición, construidos con información (individual) de agroaplicadores de Córdoba, se validaron mediante biomarcadores (actividad de butirilcolinesterasa y genotoxicidad). RESULTADOS: El área pampeana agrupa un IEP mayor al promedio nacional y los IIAT superiores, correspondientes al 2,4-D y clorpirifos. El aumento en ambos índices de exposición se asoció a incrementos en las tasas de mortalidad por cáncer a nivel departamental. El daño genotóxico en aplicadores no se asoció a los niveles de exposición; sí la disminución de la actividad de butirilcolinesterasa. CONCLUSIONES: Los instrumentos ­índices­ y resultados alcanzados brindan valiosos elementos para vigilar la exposición a plaguicidas en Argentina.

INTRODUCTION: Pesticides are a key factor of agricultural practices. OBJECTIVES: To describe the spatial distribution of pesticide exposure in Argentina and its association with cancer burden indicators, build global exposure indices, and validate individual exposure indices with biomarkers of effect in occupationally exposed subjects. METHODS: Two global indices were developed (pesticide exposure [PEI] and total environmental impact [TEII]), their spatial distribution was studied and, by means of a nationwide ecological study, the association with total, breast and prostate cancer mortality rates was estimated, using departments as level of spatial disaggregation (n=564). Two exposure indices, built with (individual) information of pesticide applicators in Córdoba, were validated using biomarkers (butyrylcholinesterase and genotoxicity). RESULTS: The Pampas have a PEI which is higher than national average as well as the highest TEII, corresponding to 2.4-D and chlorpyrifos. The increase in both exposure indices was associated to increases in the mortality rates due to cancer at the departmental level. Genotoxic damage in applicators was not associated to levels of exposure; what was associated was the reduction of butyrylcholinesterase activity. CONCLUSIONS: The instruments ­indices­ and results obtained provide valuable elements for the surveillance of pesticide exposure in Argentina.

Exposición a plaguicidas, desnutrición crónica y daño genotóxico en menores de tres años. Luribay / Pesticide exposure, chronic malnutrition and genotoxic damagein children under three years. Luribay

OBJETIVO: Evaluar si la exposición a plaguicidas y la desnutrición crónica son factores de riesgo para daño genotóxico en menores de tres años del municipio de Luribay del departamento de La Paz. Noviembre ­ 2008. MATERIAL Y MÉTODOS: estudio de casos y controles. 155 niños y niñas menores de tres años estudiados, habitantes de ocho poblaciones de Luribay, La Paz - Bolivia de las 15 intervenidas por el Programa de Crecimiento Comunitario (Save the Children). Se aplicó a las madres una encuesta validada y adaptada al lugar para medir la exposición a plaguicidas y se realizó a los niños(as) la técnica de citoma bucal para determinación del daño genotóxico. RESULTADOS: un 61% de las madres se dedicaba a la agricultura, de ellas un 33% fumigó al menos una vez estando embarazada y 85% no utiliza equipo de protección completo. 83% de los niños presentan daño genotóxico, de ellos 84% se encuentran expuestos a plaguicidas. Los niños no desnutridos y expuestos a plaguicidas con daño genotóxico alcanzan un total de 35%. No se encontraron diferencias significativas entre los grupos de no desnutridos y expuestos a plaguicidas con Daño Genotóxico y los niños desnutridos crónicos y expuestos a plaguicidas también con Daño Genotóxico, (no desnutridos p=1,00) (desnutridos crónicos p=0,70). Los resultados en relación a la diferencia de edad en los pacientes con y sin daño genotóxico, son significativos (p=0.05).

OBJECTIVE: to assess whether exposure to pesticides and chronic malnutrition are risk factors for genotoxic damage in children under three years of age, of the municipality of Luribay, Department of La Paz. November -2008. METHODS: case study and control. 155 boys and girls were studied from eight Luribay towns, La Paz -Bolivia out of 15 involved by the Communitarian Development Program (Save the Children). A survey was applied, validated and adapted to the location in order to measure pesticide exposure, and the buccal cytome technique was applied on children for determining genotoxic damage. RESULTS: 61 percent of the mothers dedicated themselves to agriculture, out of them a 33 percent had fumigated at least once being pregnant, and 85 percent did not use appropriate protective gear. 83 percent of the children have genotoxic damage, out of them 84 percent are exposed to pesticides. Non-malnourished children and exposed to pesticides with genotoxic damage reach 35 percent. No meaningful differences were found between the group of Non-malnourished children and exposed to pesticides with genotoxic damage and the chronic malnourished children and exposed to pesticides with genotoxic damage, (Non-malnourished p=1,00) ( chronic malnourished p=0,70). Results concerning age difference in patients with and without genotoxic damage are meaningful (p=0.05).

Caracterização da via dos Interferons e a via da proteína p53 em linhagens de células tumorais expostas ao dano genotóxico

O gene gbp-2 codifica uma proteína com função biológica pouco estudada, é altamente expresso após a indução de IFNγ e requer o fator de transcrição IRF-1 para sua indução. A regulação positiva de gbp-2 dependente da ativação da proteína supressora de tumor p53 foi recentemente descrita em uma linhagem de carcinoma de esôfago que expressa uma proteína mutante p53 termo-sensível. A ativação da proteína p53 por sinais de estresse, como dano ao DNA, induz genes que participam da parada do ciclo celular e apoptose. Nesse contexto, os principais objetivos dessa tese foram: (i) verificar a indução de gbp-2 após a ativação de p53 pelo dano genotóxico; (ii) correlacionar sua eventual indução com a ativação de IRF-1; (iii) correlacionar a indução de gbp-2 e de sua proteína com as respostas celulares após o dano ao DNA. Nessa tese, pela primeira vez foi demonstrado que o gene gbp-2 é induzido pelo dano genotóxico; essa indução correlacionou-se com a presença da proteína p53 selvagem em linhagens tumorais; o aumento de expressão de IRF-1 não foi suficiente para a indução de gbp-2 após o dano ao DNA; nas linhagens celulares nas quais houve a indução de gbp-2 a resposta predominante foi a de parada do ciclo celular. O estudo da relação entre a via dos IFNs e da p53 pode trazer importantes implicações do papel dos IFNs durante a carcinogênese.

The gene gbp-2 codes for a protein with an unknown biological function. Gbp-2 is highly expressed after the induction by IFNγ and requires the transcription factor IRF-1. Recently, the positive p53-dependent regulation of gbp-2 was described in an esophageal cell line, wich expresses a temperature-sensitive mutant p53. The activation of p53 by stress signal such as DNA damage is known to induce genes involved in cell cycle arrest and apoptosis. Within this context, the main objectives of this study were: (i) to evaluate gbp-2 induction upon p53 activation by genotoxic damage; (ii) to establish a correlation of an eventual gbp-2 induction with IRF-1 activation; (iii) to correlate gbp-2 induction with cellular response to DNA damage. In this study, it was demonstrated for the first time that gbp-2 may be induced by genotoxic effect and also that the induction occurred in p53wt cell lines. Furthermore it was demonstrated that an increase in the expression of IRF-1 was not sufficient to induce gbp-2 following DNA damage. In addition, within the cell lines at which a gbp-2 induction was observed the preferential response was arrest of cell cycle progression. The study of the correlation between IFN and p53 pathways may reveal important implications for the understanding of the role of IFN during carcinogenesis.