دورية أكاديمية
Lung genotoxicity of benzo(a)pyrene in vivo involves reactivation of LINE-1 retrotransposon and early reprogramming of oncogenic regulatory networks.
| العنوان: | Lung genotoxicity of benzo(a)pyrene in vivo involves reactivation of LINE-1 retrotransposon and early reprogramming of oncogenic regulatory networks. |
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| المؤلفون: | Hassanin AAI; Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona College of Medicine, Tucson, Arizona.; Department of Animal Wealth Development, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt., Tavera-Garcia M; Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona College of Medicine, Tucson, Arizona., Moorthy B; Department of Pediatrics, Baylor College of Medicine, Houston, Texas., Zhou GD; Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, Texas., Ramos KS; Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona College of Medicine, Tucson, Arizona.; Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, Texas. |
| المصدر: | American journal of physiology. Lung cellular and molecular physiology [Am J Physiol Lung Cell Mol Physiol] 2019 Dec 01; Vol. 317 (6), pp. L816-L822. Date of Electronic Publication: 2019 Oct 09. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901229 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1504 (Electronic) Linking ISSN: 10400605 NLM ISO Abbreviation: Am J Physiol Lung Cell Mol Physiol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Bethesda, MD : American Physiological Society, c1989- |
| مواضيع طبية MeSH: | DNA Damage* , Gene Regulatory Networks*, Benzo(a)pyrene/*toxicity , Long Interspersed Nucleotide Elements/*genetics , Lung/*pathology , Lung Neoplasms/*pathology , Transgenes/*physiology, Animals ; Carcinogens/toxicity ; Cellular Reprogramming ; Humans ; Integrases/metabolism ; Lung/drug effects ; Lung/metabolism ; Lung Neoplasms/chemically induced ; Lung Neoplasms/genetics ; Mice |
| مستخلص: | Several lines of evidence have implicated long interspersed nuclear element-1 (LINE-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, whereas retrotransposition-independent mechanisms disrupt epithelial programming and differentiation. Previous work by our group established that tobacco carcinogens such as benzo(a)pyrene (BaP) reactivate LINE-1 in bronchial epithelial cells through displacement of nucleosome remodeling and deacetylase (NuRD) corepressor complexes and interference with retinoblastoma-regulated epigenetic signaling. Whether LINE-1 in coordination with other genes within its regulatory network contributes to the in vivo genotoxic response to BaP remains largely unknown. Evidence is presented here that intratracheal instillation of ORFeus LSL 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 compared with males and synergized by adeno-CRE recombinase. This is the first report linking LINE-1 and genes within its oncogenic regulatory network with early sexually dimorphic responses of the lung in vivo. |
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| معلومات مُعتمدة: | R01 ES009132 United States ES NIEHS NIH HHS; R01 HL129794 United States HL NHLBI NIH HHS; P42 ES027725 United States ES NIEHS NIH HHS; P30 ES030285 United States ES NIEHS NIH HHS; R01 ES029382 United States ES NIEHS NIH HHS |
| فهرسة مساهمة: | Keywords: LINE-1; ORFeusLSL; benzo(a)pyrene; lung; oncogenic reprogramming |
| المشرفين على المادة: | 0 (Carcinogens) 3417WMA06D (Benzo(a)pyrene) EC 2.7.7.- (Cre recombinase) EC 2.7.7.- (Integrases) |
| تواريخ الأحداث: | Date Created: 20191010 Date Completed: 20200407 Latest Revision: 20220507 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC6962597 |
| DOI: | 10.1152/ajplung.00304.2019 |
| PMID: | 31596105 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1522-1504 |
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| DOI: | 10.1152/ajplung.00304.2019 |