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Epigenetic mechanisms of nickel carcinogenesis
1Nelson Institute of Environmental Medicine and Kaplan Comprehensive Cancer Center, New York University School of Medicine, NY 10016, USA.
Abstract:
This article considers the mechanism of nickel carcinogenesis, focusing primarily on the epigenetic changes associated with exposure of cells to carcinogenic nickel compounds. We discuss the delivery of nickel in the cell and contrast the genetic and epigenetic changes that have occurred. Within the epigenetic effects, alteration in the levels of transcription factors, such as ATF-1, p53, HIF-1, HIF-1alpha, and NFkappaB, are considered. The relationship between nickel and calcium metabolism and the role it plays in nickel carcinogenesis is also considered, as are reactive oxygen species and the interactions of nickel with proteins. We discuss these epigenetic discussions in light of the effects that nickel has on inducing DNA methylation in cells. It is of interest that nickel induces both a variety of signaling pathways as well as genes that seem to be important for the survival of cancer cells. It is also interesting that the same genes induced or repressed by nickel are similarly overexpressed or not expressed in nickel-transformed cells. It is suggested that this may represent a selection process crucial to the nickel carcinogenesis process.
Insights
Nickel exposure triggers epigenetic changes, including DNA methylation and altered transcription factors, driving nickel carcinogenesis. These changes influence cell survival pathways, crucial for cancer development.
Area of Science:
- Environmental Toxicology
- Molecular Biology
- Cancer Research
Background:
- Nickel compounds are known carcinogens.
- Understanding nickel carcinogenesis mechanisms is crucial for risk assessment and prevention.
Purpose of the Study:
- To elucidate the epigenetic mechanisms underlying nickel-induced carcinogenesis.
- To identify key molecular players and pathways involved in nickel's carcinogenic effects.
Main Methods:
- Review of existing literature on nickel toxicology and epigenetics.
- Analysis of epigenetic alterations, including DNA methylation and transcription factor modulation.
- Examination of nickel's interaction with cellular processes like calcium metabolism and reactive oxygen species.
Main Results:
- Nickel exposure induces significant epigenetic changes, notably DNA methylation.
- Alterations in transcription factors (e.g., ATF-1, p53, HIF-1, NFkappaB) are linked to nickel carcinogenesis.
- Nickel influences cell signaling pathways and genes critical for cancer cell survival.
Conclusions:
- Epigenetic modifications, particularly DNA methylation, are central to nickel carcinogenesis.
- Nickel-induced changes in gene expression and signaling pathways contribute to cancer cell survival and progression.
- A selection process involving specific gene expression patterns may be critical in nickel-induced cancer development.