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Publication Detail

Title: GeneChip analysis of signaling pathways effected by nickel.

Authors: Salnikow, Konstantin; Davidson, Todd; Kluz, Thomas; Chen, Haobin; Zhou, Daoji; Costa, Max

Published In J Environ Monit, (2003 Apr)

Abstract: The carcinogenicity of nickel compounds has been shown in numerous epidemiological and animal studies. Carcinogenesis is generally considered as a multistep accumulation of genetic alterations. Nickel, however, being highly carcinogenic is only a weak mutagen. We hypothesize that nickel may act by modulating signaling pathways, and subsequently by reprogramming transcription factors. Insoluble nickel is considered to be more carcinogenic than soluble. In this study using GeneChip technology we compared changes in gene expression caused by soluble and insoluble nickel compounds. We found that both soluble and insoluble nickel compounds induce similar signaling pathways following 20 h of in vitro exposure. For example, both nickel compounds activated a number of transcription factors including hypoxia-inducible factor I (HIF-1) and p53. The induction of these important transcription factors exerts potent selective pressure leading to cell transformation. The obtained data are in agreement with our previous observations that acute nickel exposure activates HIF-1 and p53 transcription factors and in nickel-transformed cells, the ratio of HIF-I activity to p53 activity was shifted towards high HIF-I activity. The activation of the same signaling pathways by soluble and insoluble nickel compounds suggested that both nickel compounds have similar carcinogenic potential in vitro.

PubMed ID: 12729255 Exiting the NIEHS site

MeSH Terms: Animals; Cell Culture Techniques; Cell Transformation, Neoplastic*; Embryo, Mammalian; Fibroblasts; Gene Expression Profiling*; Mice; Neoplasms/physiopathology; Nickel/adverse effects*; Nickel/chemistry; Oligonucleotide Array Sequence Analysis*; Signal Transduction; Solubility; Transcription Factors; Tumor Suppressor Protein p53/biosynthesis

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