Lung Genotoxicity of Benzo(a)Pyrene in Vivo Involves Reactivation of LINE-1 Retrotransposon and Reprogramming ofOncogenic Regulatory Networks.

Lung Genotoxicity of Benzo(a)Pyrene in Vivo Involves Reactivation of LINE-1 Retrotransposon and Reprogramming ofOncogenic Regulatory Networks. Am J Physiol Lung Cell Mol Physiol. 2019 Oct 09;: Authors: Hassanin AA, Tavera-Garcia M, Moorthy B, Zhang GD, Ramos KS Abstract Several lines of evidence have implicated LINE-1 (Long INterspersed nuclear Element-1) retroelement in the onset and progression of lung cancer. Retrotransposition-dependent mechanisms leading to DNA mobilization give rise to insertion mutations and DNA deletions, while retrotransposition-independent mechanisms disrupt epithelial programming and differentiation. Previous work by our group established that tobacco carcinogens like benzo(a)pyrene (BaP) reactivate LINE-1 in bronchial epithelial cells through displacement of NuRD corepressor complexes and interference with retinoblastoma-regulated epigenetic signaling. Whether LINE-1 in coordination with other genes within its regulatory network contribute to the in vivo genotoxic response to BaP remains largely unknown. Evidence is presented here that intratracheal instillation of ORFEUSLSL mice with BaP alone or in combination with adenovirus (adeno) CRE recombinase is genotoxic to the lung and associated with activation of the human LINE-1 transgene present in these mice. LINE-1 reactivation modulated the expression of genes involved in oncogenic signaling and these responses were most pronounced in female mice compare...
Source: Am J Physiol Lung Ce... - Category: Respiratory Medicine Authors: Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research