Altered gene expression in human cells induced by the agricultural chemical Enable

Abstract

Steroid hormones bind to highly specific nuclear receptors, regulating gene expression that results in normal fetal growth and development and/or in normal adult physiological function. Many industrial and agricultural chemicals may bind one or more nuclear receptors, acting as mimics of steroid hormones, and are called endocrine disruptive chemicals (EDC) because they alter the expression of endocrine-regulated genes. A widely used fungicide, Enable (fenbuconazole), was evaluated to examine its capacity to alter endocrine-regulated gene expression. Cells of an oestrogen-dependent human breast cancer-derived line, MCF-7, were treated with a range, 0.033-3.3 ppb (ng/mL), of Enable, and gene expression was compared to that of untreated cells. Microarray analysis using a chip with 600 gene spots showed downregulation of eight genes and upregulation of 34 genes in cells treated with 3.3 ppb of Enable, compared to untreated cells. Specific genes were selected for consideration. Real-time PCR confirmed results obtained from analysis of the microarray data for the genes phenol sulphotransferase (PST), intercellular adhesion molecule-1 (ICAM-1), transforming growth factor beta-3 (TGF beta-3) and calreticulin. These studies were designed to provide base-line data on the gene expression-altering capacity of a specific chemical at a low dose, and will allow assessment of the possible deleterious effects that may be caused in human cells by exposure to the agricultural chemical Enable.