Exposure to metals not only induces physiological toxic responses but also increases the risk of cancer incidence. Lung is one of the target organs of toxicant exposure and elimination. This study aimed to evaluate the toxic effect of metals on lung cancer cells using colorimetric cDNA microarray. Human lung adenocarcinoma cells (CL3) were treated with antimony, arsenite, arsenate, lead, cadmium, copper or nickel for 24 h under the dosage responsible for 70% cell survival by clonogenic assay. A set of notably affected metal-responsive genes (46 genes, 6.5% of assayed genes) showed that the percentages of genes related to metabolism were decreased compared to original array, whereas those of genes associated with cell cycle and cell proliferation were increased. Hierarchical cluster analysis revealed that antimony, arsenate, arsenite and lead induced similar gene expression profiles; cadmium and copper mediated another profile group, while a distinct expression pattern was induced by nickel. The transcripts of two drug-metabolizing enzymes, namely NAD(P)H:quinone reductase (NQO1) and heme oxygenase 1 (HMOX1), were significantly enhanced by all seven metals. In contrast, no overlapped genes were down-regulated. Nickel compounds are human carcinogen of lung cancer. Nickel treatment specifically affected the expression activity of several oncogenic-related genes such as placental growth factor (PGF), colony stimulating factor 1 receptor (CSF1R), and thrombomodulin (THBD). Our data thus suggest that phase II enzymes may be essential for detoxification or cytoprotection of metal-challenged lung cells, and highlight the tumorigenic role of nickel in human lung cells.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]