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Measurement of Telomere Length and Regulatory Genes in Circulating Peripheral Blood Monocytes and Lung Tissue as a Biomarker for Response After Inhalation Exposure to Occupational Particles
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A1928 - Measurement of Telomere Length and Regulatory Genes in Circulating Peripheral Blood Monocytes and Lung Tissue as a Biomarker for Response After Inhalation Exposure to Occupational Particles
Author Block: M. Shoeb, V. K. Kodali, G. M. Mustafa, B. Y. Farris, K. A. Roach, K. Smith, T. Meighan, C. Umbright, J. R. Roberts, P. Joseph, A. Erdely, J. Antonini; HELD, CDC/NIOSH, Morgantown, WV, United States.
The measurement of telomere length may serve as a potential biomarker to assess occupational exposure. Telomeres are simple repetitive structures of DNA sequences (TTAGGG)n that stabilize ends of chromosomes by preventing DNA degradation and preserving genetic information. Telomeres generally shorten with age, and their length may be influenced by stressors, such as occupational exposures. The goal of the study was to measure telomere length and genes involved in regulation [e.g., regulator of telomere length-1 (RTEL1) and telomerase reverse transcriptase (TERT)] in peripheral blood monocytes (PBMCs) and in lung tissue after exposure to different workplace particles in an animal model. Using different exposure paradigms, whole blood, PBMCs and lung tissue were collected from male Fischer-344 rats: (1) at 1 d and 12 wk after inhalation to 20 mg/m3 x 3 hr/d x 4 d/wk x 5 wk of stainless steel welding fume (SS-WF) and (2) at 4, 32, and 44 wk after inhalation to 15 mg/m3 x 6 h/d x 5 d of silica (Si). In both paradigms, control animals were exposed to filtered air. SS-WF inhalation caused a significant decrease in telomere length in circulating PBMCs and in lung tissue over the 12 wk time course compared to control. On the other hand, telomere length was significantly increased in lung tissue in the Si-exposed group at 4 and 32 wk compared to control. No significant changes were observed in telomere length of blood cells recovered from the Si-exposed group. Importantly, RTEL1 expression was significantly decreased in lung tissue of the Si-exposed animals at all-time points compared to control, whereas TERT expression was significantly increased at 4 and 32 wk. Thus, varied responses in regards to telomere length and regulation were observed after different occupational exposures and were specific for the agent. Telomere length and expression of telosome and regulatory genes may serve as potential biomarkers related to occupational exposure and may offer insight into the molecular mechanism of particle-induced lung disease.
Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the NIOSH.
Conference: American Thoracic Society Annual Meeting, May 18-23, 2018, San Diego, CA
Keywords: Silica, welding fume, DNA damage, inhalation toxicology, biomarker
Author Block: M. Shoeb, V. K. Kodali, G. M. Mustafa, B. Y. Farris, K. A. Roach, K. Smith, T. Meighan, C. Umbright, J. R. Roberts, P. Joseph, A. Erdely, J. Antonini; HELD, CDC/NIOSH, Morgantown, WV, United States.
The measurement of telomere length may serve as a potential biomarker to assess occupational exposure. Telomeres are simple repetitive structures of DNA sequences (TTAGGG)n that stabilize ends of chromosomes by preventing DNA degradation and preserving genetic information. Telomeres generally shorten with age, and their length may be influenced by stressors, such as occupational exposures. The goal of the study was to measure telomere length and genes involved in regulation [e.g., regulator of telomere length-1 (RTEL1) and telomerase reverse transcriptase (TERT)] in peripheral blood monocytes (PBMCs) and in lung tissue after exposure to different workplace particles in an animal model. Using different exposure paradigms, whole blood, PBMCs and lung tissue were collected from male Fischer-344 rats: (1) at 1 d and 12 wk after inhalation to 20 mg/m3 x 3 hr/d x 4 d/wk x 5 wk of stainless steel welding fume (SS-WF) and (2) at 4, 32, and 44 wk after inhalation to 15 mg/m3 x 6 h/d x 5 d of silica (Si). In both paradigms, control animals were exposed to filtered air. SS-WF inhalation caused a significant decrease in telomere length in circulating PBMCs and in lung tissue over the 12 wk time course compared to control. On the other hand, telomere length was significantly increased in lung tissue in the Si-exposed group at 4 and 32 wk compared to control. No significant changes were observed in telomere length of blood cells recovered from the Si-exposed group. Importantly, RTEL1 expression was significantly decreased in lung tissue of the Si-exposed animals at all-time points compared to control, whereas TERT expression was significantly increased at 4 and 32 wk. Thus, varied responses in regards to telomere length and regulation were observed after different occupational exposures and were specific for the agent. Telomere length and expression of telosome and regulatory genes may serve as potential biomarkers related to occupational exposure and may offer insight into the molecular mechanism of particle-induced lung disease.
Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the NIOSH.
Conference: American Thoracic Society Annual Meeting, May 18-23, 2018, San Diego, CA
Keywords: Silica, welding fume, DNA damage, inhalation toxicology, biomarker
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