Response of transposable elements to environmental stressors.
Transposable elements (TEs) comprise a group of repetitive sequences that bring positive, negative, as well as neutral effects to the host organism. Earlier considered as "junk DNA," TEs are now well-accepted driving forces of evolution and critical regulators of the expression of genetic information. Their activity is regulated by epigenetic mechanisms, including methylation of DNA and histone modifications. The loss of epigenetic control over TEs, exhibited as loss of DNA methylation and decondensation of the chromatin structure, may result in TEs reactivation, initiation of their insertional mutagenesis (retrotransposition) and has been reported in numerous human diseases, including cancer. Accumulating evidence suggests that these alterations are not the simple consequences of the disease, but often may drive the pathogenesis, as they can be detected early during disease development. Knowledge derived from the in vitro, in vivo, and epidemiological studies, clearly demonstrates that exposure to ubiquitous environmental stressors, many of which are carcinogens or suspected carcinogens, are capable of causing alterations in methylation and expression of TEs and initiate retrotransposition events. Evidence summarized in this review suggests that TEs are the sensitive endpoints for detection of effects caused by such environmental stressors, as ionizing radiation (terrestrial, space, and UV-radiation), air pollution (including particulate matter [PM]-derived and gaseous), persistent organic pollutants, and metals. Furthermore, the significance of these effects is characterized by their early appearance, persistence and presence in both, target organs and peripheral blood. Altogether, these findings suggest that TEs may potentially be introduced into safety and risk assessment and serve as biomarkers of exposure to environmental stressors. Furthermore, TEs also show significant potential to become invaluable surrogate biomarkers in clinic and possible targets for therapeutic modalities for disease treatment and prevention.
Department of Environmental and Occupational Health, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. Electronic address: iracinemiousse@uams.edu.
Isabelle R
IR
Miousse
Department of Environmental and Occupational Health, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. Electronic address: mgchalbot@uams.edu.
Marie-Cecile G
MC
Chalbot
Division of Biochemical Toxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA. Electronic address: annie.lumen@fda.hhs.gov.
Annie
A
Lumen
Department of Environmental and Occupational Health, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. Electronic address: aferguson@uams.edu.
Alesia
A
Ferguson
Department of Environmental and Occupational Health, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. Electronic address: ikavouras@uams.edu.
Ilias G
IG
Kavouras
Department of Environmental and Occupational Health, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. Electronic address: ikoturbash@uams.edu.
Igor
I
Koturbash
D015415:Biomarkers / Q000378:metabolism; D019175:DNA Methylation; D004251:DNA Transposable Elements / Q000187:drug effects / Q000528:radiation effects; D004785:Environmental Pollutants / Q000633:toxicity*; D044127:Epigenesis, Genetic; D006801:Humans; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics
D015415:Biomarkers; D004251:DNA Transposable Elements; D004785:Environmental Pollutants
Air pollution; DNA methylation; Environmental stressors; Ionizing radiation; Metals; Retrotransposition