Human drug metabolism genes in parathion-and estrogen-treated breast cells

Abstract

Abstract. Environmental chemicals may be involved in the etiology of breast cancer. Among them, organophosphorous compounds are the most widely used pesticides because of their extensive use in agriculture, medicine and industry. The risk of breast cancer is associated with prolonged exposure to female hormones and is attributed to estrogen since prolonged stimulation by steroid hormones may increase cell division. The aim of the present study was to identify the differentially expressed genes encoding enzymes that are important to drug transport and metabolism in parathion-and estrogen-treated human breast epithelial cell lines using cDNA microarrays. MCF-l0F, an immortalized human breast epithelial cell line was treated with parathion and estrogen, either alone or in combination, and malignant cells were developed through a series of sequential steps. Differential expression from the drug metabolism gene array showed that 17 genes were found to be altered either by parathion or estrogen alone, or the combination of both. Among the genes altered by parathion in comparison to the control were CHST5, CHST6 and CHST7 (sulfotransferases); CYP2F1, CYP3A7 and CYP4F3 (CYPs); GSTP1, GSTT2 and MGST1 (GSTs); MT1X (metallothionein); TPMT (methyltransferase); UGT1A1 and UGT2B (UDP glycosyltransferases). The same genes were down-regulated in estrogen alone including several metallothioneins (MT1A, MT1E, MT1H, MT1L and MT2A). The combination of parathion and estrogen induced downregulation of three sulfotransferases, CYP2F1 and CYP4F3, MGST1, all metallothioneins and TPMT genes. There was no change in CYP3A7, GSTP1, GSTT2, UGT1A1 and UGT2B genes in the presence of both substances. It can be concluded from this study that organophosphorous pesticides such as parathion in the presence of estradiol induced changes in human drug metabolism gene expression in breast cells.

Carcinogenicity of Malathion and Estrogen in an Experimental Rat Mammary Gland Model

“…Knowledge of factors that control cell proliferation of normal and neoplastic mammary epithelium, and the molecular basis of such action, is essential for a deeper understanding of the progression of human breast cancer. In rat mammary gland models whereby individual neoplastic transformed stages can be dissected and studied provide an excellent opportunity to address cellular and molecular mechanisms involved in environmental-induced mammary carcinogenesis [6].…”

LSOSS: Detection of Cancer Outlier Differential Gene Expression

“…The numbers of breast cancer related genes identified by existing methods (Table 1) were 8, 8, 4, 3, and 2 for MOST, ORT, OS, the t -statistics, and COPA, respectively. However, our proposed method (LSOSS) has identified 9 breast cancer related genes: KCNH2,7 NEO1,8 MAGEA3,9 ENG,10 GABRG2,11 ATM,12 NUP88,13 CYP3A714 and PMP22 15. Although it should not be treated as a golden standard method for evaluating different statistical tools, this type of analysis generally validates the statistical results and highlights their biological relevance.…”

Plaguicidas organofosforados y cáncer en Latinoamérica: Evidencia para una discusión bioética

“…En ella se observa que todos los estudios analizados encontraron una relación dosis-respuesta a OP. De estos, nueve clasificaron en un nivel de calidad alto, correspondiendo a investigaciones experimentales sobre exposición controlada a malatión, paratión y clorpirifos y desarrollo de cáncer mamario en tejido humano, realizadas en Chile y Argentina (Cabello, Juarranz, Botella y Calaf, 2003;Calaf y Roy, 2007a;Calaf y Roy, 2007b;Calaf y Roy, 2007c;Calaf y Roy, 2008a;Calaf y Roy, 2008b;Calaf, Echiburu-Chay y Roy, 2009;Ventura et al, 2012).…”

“…Los estudios realizados en Latinoamérica demuestran que la exposición a plaguicidas OP se asocia con cáncer. De los 11 artículos que cumplieron con los criterios de elegibilidad, nueve midieron exposición a plaguicidas OP a través de células humanas tratadas directamente con OP y son de alta calidad en el desarrollo de la investigación y en el control de sesgos Calaf y Roy, 2007a;Calaf y Roy, 2007b;Calaf y Roy, 2007c;Calaf y Roy, 2008a;Calaf y Roy, 2008b;Calaf et al, 2009;Ventura et al, 2012). Dentro de estas pág.…”

“…El segundo reporte (Calaf y Roy, 2007b), evidencia alteración en 17 genes, ya sea por paratión o estrógenos por separado o por la combinación de ambos, concluyendo que, en presencia de estradiol, pesticidas OP como el paratión inducen cambios en la expresión del gen humano del metabolismo en las células mamarias. Una tercera publicación (Calaf y Roy, 2007c), analiza los efectos de 17β-estradiol (E2) y el paratión en la transformación de células epiteliales mamarias in vitro, informando que este pesticida por si solo o en combinación con E2 induce transformación maligna en células MCF-10F, la que es confirmada pág.…”