Microarray analysis of gene expression patterns in human proximal tubule cells over a short and long time course of...

Numerous studies showed that renal proximal tubules cells are the cell type critically affected by chronic exposure to cadmium (Cd(2+)). The aim of the present study was to apply global gene expression technology and a human renal epithelial cell culture model (HPT) to determine whether time of exposure to Cd(2+) exerts a major influence on the resulting pattern of global gene expression. HPT cells were exposed to Cd(2+) for a short, 1-d, period of exposure (9, 27, and 45 μM) versus a longer, 13-d, period (4.5, 9, and 27 μM), with the hypothesis being that the stress response of the cells would be more active during the short time of exposure. The results showed that the differential expression of genes was very extensive for HPT cells exposed to Cd(2+) for 1 d, with more than 1848 genes displaying alterations compared to control and with the major categories of genes being involved in stress responses; cell death; checkpoint arrest, DNA repair, and the cell cycle; inflammatory responses; and cell adhesion, motion and differentiation. In contrast, HPT cells exposed to Cd(2+) for 13 d showed 923 genes to be differentially expressed, with a marked reduction in the number of differentially expressed stress response genes and a significant increase in the number of genes involved in development and differentiation. There were 387 differentially expressed genes common to both times of exposure. Data suggest that unless one is actively seeking to study the acute stress response, global gene expression technology should not be applied within an early time course of toxicant exposure.