Proteomic analysis of cellular responses to low concentration N-methyl-N'-nitro-N-nitrosoguanidine in human amnion FL cells.

We have shown previously that exposure to a low concentration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induces comprehensive changes in the protein expression profile of human amnion FL cells, including the induction, suppression, upregulation, and downregulation of various proteins. In addition, by proteomic analysis combining two-dimensional gel electrophoresis (2-DE) and mass spectrometry, some of the induced and suppressed proteins were identified. In this study, we identified an additional 18 proteins among those that were either up- or downregulated by MNNG treatment. The proteins identified were a heterogeneous group that included several zinc finger proteins, proteins involved in signal transduction, cytoskeletal proteins, cell-cycle regulation proteins, and proteins with unknown functions. The involvement of these proteins in the cellular responses to alkylating agents has not been reported before and their physiological relevance is not clear. Therefore, our findings may help better understand the global cellular stress responses to chemical carcinogens, and may lead to new studies on the functions of these MNNG-responsive proteins. Furthermore, some of these proteins may serve as biomarkers for detecting exposure of human populations to environmental carcinogens. Copyright 2004 Wiley-Liss, Inc.