Heavy metals stimulate human LINE-1 retrotransposition.
Heavy metals stimulate human LINE-1 retrotransposition.
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DOI：
10.3390/ijerph2005010014
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发表时间：
2005-04
影响因子：
--
通讯作者：
Roy-Engel AM
中科院分区：
文献类型：
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作者：
Kale SP;Moore L;Deininger PL;Roy-Engel AM
L1和Alu元件是人类基因组中最活跃的反转录子（移动的元件）。几种人类疾病，包括某些形式的乳腺癌和白血病，与基因组功能重要区域的L1和Alu插入有关。我们目前的数据表明，环境污染物，如重金属，可以刺激L1逆转录转座在组织培养系统中使用两种不同类型的检测。当使用具有稳定整合的L1载体（基因组）的细胞系或通过瞬时转染（游离型）细胞引入L1载体时，对这些试剂的反应是等效的。可再现的结果表明，汞（HgS）、镉（CdS）和镍（NiO）使L1的活性平均增加三（3）倍p<0.001。这一观察结果是第一次将几种致癌剂与L1的反转录转座活性增加联系起来，作为产生基因组不稳定性的替代机制，有助于致癌过程。我们的研究结果表明，移动的元件激活必须被认为是评估基因组损伤/不稳定性响应环境因素的机制之一。
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.