LINE-1

The LINE-1 (long interspersed nuclear element) (L1) retrotransposon is the only active and, consequently, the most important human mobile element. When activated and mobilized L1 can alter genome by induction of DNA breaks, gene disruption, altered splicing, increased frequency of recombinations, and transcriptional deregulation. Occasional insertions have disrupted gene expression and caused human disease. Due to a serious threat to genomic integrity, organisms have developed several distinct ways to keep L1 silent, and its expression in normal somatic cells is for the most part undetectable. However, reactivation of L1 has been seen in disease states, including cancer. In addition, reactivation of L1 has been observed upon in vitro and in vivo exposures to different forms of stress, such as DNA-damaging agents and environmental carcinogens. These observations are of major clinical relevance, since reactivation of L1 by environmental exposures could lead to genomic instability and disease. Given the strong influence of endogenous and environmental factors in the reactivation of L1, gaining insight into the possible roles of chemicals in the regulation of L1 expression and disease phenotypes remains a significant toxicological challenge.