Title

Heavy Metals Stimulate Human LINE-1 Retrotransposition.

Funding Source

National Institutes of Environmental and Health Sciences, National Institutes of Health, State of Louisiana Board of Reagents Support Fund

Grant Number

1S11ES09996 (SPK and PLD), RO1 GM45668 (PLD), EPS-034611 (PLD), P20 RR020152 (AMR-E and PLD)

Department

Department of Biology

Document Type

Article

Publication Date

2-6-2005

Abstract

L1 and Alu elements are among the most active retroposons (mobile elements) in the human genome. Several human diseases, including certain forms of breast cancer and leukemia, are associated with L1 and Alu insertions in functionally important areas of the genome. We present data demonstrating that environmental pollutants, such as heavy metals, can stimulate L1 retrotransposition in a tissue culture system using two different types of assays. The response to these agents was equivalent when using a cell line with a stably integrated L1 vector (genomic) or a by introducing the L1 vector by transient transfection (episomal) of the cell. Reproducible results showed that mercury (HgS), cadmium (CdS), and nickel (NiO) increase the activity of L1 by an average of three (3) fold p<0.001. This observation is the first to link several carcinogenic agents with the increased retrotransposition activity of L1 as an alternate mechanism of generating genomic instability contributing to the process of carcinogenesis. Our results demonstrate that mobile element activation must be considered as one of the mechanisms when evaluating genomic damage/instability in response to environmental agents.

Comments

DOI: 10.3390/ijerph2005010014

Acknowledgements

This research was supported by National Institutes of Environmental and Health Sciences ARCH grant, 1S11ES09996 (SPK and PLD) NIH RO1 GM45668 (PLD), NSF EPS-034611 (PLD), the State of Louisiana Board of Reagents Support Fund (PLD) and NIH P20 RR020152 (AMR-E and PLD).

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