Heavy Metals Stimulate Human LINE-1 Retrotransposition.
National Institutes of Environmental and Health Sciences, National Institutes of Health, State of Louisiana Board of Reagents Support Fund
1S11ES09996 (SPK and PLD), RO1 GM45668 (PLD), EPS-034611 (PLD), P20 RR020152 (AMR-E and PLD)
Department of Biology
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.
Ireland, Shubha Kale; Moore, L.; Deininger, P. L.; and Roy-Engel, Astrid M., "Heavy Metals Stimulate Human LINE-1 Retrotransposition." (2005). Faculty and Staff Publications. 178.