Environmentally induced ribosomal DNA (rDNA) instability in human cells and populations exposed to hexavalent chromium [Cr (VI)]
Hexavalent Chromium [Cr (VI)] is an established toxicant, carcinogen, and a significant source of public health concern. The multicopy ribosomal DNA (rDNA) array is mechanistically linked to aging and cancer, is the most evolutionarily conserved segment of the human genome, and gives origin to nucle...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-08-01
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| Series: | Environment International |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412021001501 |
| _version_ | 1830491262009999360 |
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| author | Jianlin Lou Shoukai Yu Lingfang Feng Xinnian Guo Meng Wang Alan T. Branco Tao Li Bernardo Lemos |
| author_facet | Jianlin Lou Shoukai Yu Lingfang Feng Xinnian Guo Meng Wang Alan T. Branco Tao Li Bernardo Lemos |
| author_sort | Jianlin Lou |
| collection | DOAJ |
| description | Hexavalent Chromium [Cr (VI)] is an established toxicant, carcinogen, and a significant source of public health concern. The multicopy ribosomal DNA (rDNA) array is mechanistically linked to aging and cancer, is the most evolutionarily conserved segment of the human genome, and gives origin to nucleolus, a nuclear organelle where ribosomes are assembled. Here we show that exposure to Cr (VI) induces instability in the rDNA, triggering cycles of rapid, specific, and transient amplification and contraction of the array in human cells. The dynamic of environmentally responsive rDNA copy number (CN) amplification and contraction occurs at doses to which millions of individuals are regularly exposed. Finally, analyses of human populations occupationally exposed to Cr (VI) indicate that environmental exposure history and drinking habits but not age shape extensive naturally occurring rDNA copy number variation. Our observations identify a novel pathway of response to hexavalent chromium exposure and raise the prospect that a suite of environmental determinants of rDNA copy number remain to be discovered. |
| first_indexed | 2024-12-21T20:07:07Z |
| format | Article |
| id | doaj.art-e9aa6865fbcf4be7afc5fbaa7de29ea0 |
| institution | Directory Open Access Journal |
| issn | 0160-4120 |
| language | English |
| last_indexed | 2024-12-21T20:07:07Z |
| publishDate | 2021-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Environment International |
| spelling | doaj.art-e9aa6865fbcf4be7afc5fbaa7de29ea02022-12-21T18:51:49ZengElsevierEnvironment International0160-41202021-08-01153106525Environmentally induced ribosomal DNA (rDNA) instability in human cells and populations exposed to hexavalent chromium [Cr (VI)]Jianlin Lou0Shoukai Yu1Lingfang Feng2Xinnian Guo3Meng Wang4Alan T. Branco5Tao Li6Bernardo Lemos7Program in Molecular and Integrative Physiological Sciences & Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, USA; School of Public Health, Hangzhou Medical College, Hangzhou, People’s Republic of China; Institute of Occupational Diseases, Zhejiang Academy of Medical Sciences, Hangzhou, People’s Republic of ChinaProgram in Molecular and Integrative Physiological Sciences & Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, USASchool of Public Health, Hangzhou Medical College, Hangzhou, People’s Republic of China; Institute of Occupational Diseases, Zhejiang Academy of Medical Sciences, Hangzhou, People’s Republic of ChinaSchool of Public Health, Hangzhou Medical College, Hangzhou, People’s Republic of China; Institute of Occupational Diseases, Zhejiang Academy of Medical Sciences, Hangzhou, People’s Republic of ChinaProgram in Molecular and Integrative Physiological Sciences & Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, USAProgram in Molecular and Integrative Physiological Sciences & Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, USASchool of Public Health, Hangzhou Medical College, Hangzhou, People’s Republic of China; Institute of Occupational Diseases, Zhejiang Academy of Medical Sciences, Hangzhou, People’s Republic of ChinaProgram in Molecular and Integrative Physiological Sciences & Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, USA; Corresponding author at: Harvard T. H. Chan School of Public Health, 665 Huntington Ave, Boston, MA 02115, USA.Hexavalent Chromium [Cr (VI)] is an established toxicant, carcinogen, and a significant source of public health concern. The multicopy ribosomal DNA (rDNA) array is mechanistically linked to aging and cancer, is the most evolutionarily conserved segment of the human genome, and gives origin to nucleolus, a nuclear organelle where ribosomes are assembled. Here we show that exposure to Cr (VI) induces instability in the rDNA, triggering cycles of rapid, specific, and transient amplification and contraction of the array in human cells. The dynamic of environmentally responsive rDNA copy number (CN) amplification and contraction occurs at doses to which millions of individuals are regularly exposed. Finally, analyses of human populations occupationally exposed to Cr (VI) indicate that environmental exposure history and drinking habits but not age shape extensive naturally occurring rDNA copy number variation. Our observations identify a novel pathway of response to hexavalent chromium exposure and raise the prospect that a suite of environmental determinants of rDNA copy number remain to be discovered.http://www.sciencedirect.com/science/article/pii/S0160412021001501ChromiumRibosomerDNANucleolusCopy number |
| spellingShingle | Jianlin Lou Shoukai Yu Lingfang Feng Xinnian Guo Meng Wang Alan T. Branco Tao Li Bernardo Lemos Environmentally induced ribosomal DNA (rDNA) instability in human cells and populations exposed to hexavalent chromium [Cr (VI)] Environment International Chromium Ribosome rDNA Nucleolus Copy number |
| title | Environmentally induced ribosomal DNA (rDNA) instability in human cells and populations exposed to hexavalent chromium [Cr (VI)] |
| title_full | Environmentally induced ribosomal DNA (rDNA) instability in human cells and populations exposed to hexavalent chromium [Cr (VI)] |
| title_fullStr | Environmentally induced ribosomal DNA (rDNA) instability in human cells and populations exposed to hexavalent chromium [Cr (VI)] |
| title_full_unstemmed | Environmentally induced ribosomal DNA (rDNA) instability in human cells and populations exposed to hexavalent chromium [Cr (VI)] |
| title_short | Environmentally induced ribosomal DNA (rDNA) instability in human cells and populations exposed to hexavalent chromium [Cr (VI)] |
| title_sort | environmentally induced ribosomal dna rdna instability in human cells and populations exposed to hexavalent chromium cr vi |
| topic | Chromium Ribosome rDNA Nucleolus Copy number |
| url | http://www.sciencedirect.com/science/article/pii/S0160412021001501 |
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