Cargando…
Low-dose exposure to PBDE disrupts genomic integrity and innate immunity in mammary tissue
The low-dose mixture hypothesis of carcinogenesis proposes that exposure to an environmental chemical that is not individually oncogenic may nonetheless be capable of enabling carcinogenesis when it acts in concert with other factors. A class of ubiquitous environmental chemicals that are hypothesiz...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9413140/ https://www.ncbi.nlm.nih.gov/pubmed/36035174 http://dx.doi.org/10.3389/fgene.2022.904607 |
_version_ | 1784775666765398016 |
---|---|
author | Lamkin, Donald M. Chen, Shiuan Bradshaw, Karen P. Xu, Shili Faull, Kym F. Sloan, Erica K. Cole, Steve W. |
author_facet | Lamkin, Donald M. Chen, Shiuan Bradshaw, Karen P. Xu, Shili Faull, Kym F. Sloan, Erica K. Cole, Steve W. |
author_sort | Lamkin, Donald M. |
collection | PubMed |
description | The low-dose mixture hypothesis of carcinogenesis proposes that exposure to an environmental chemical that is not individually oncogenic may nonetheless be capable of enabling carcinogenesis when it acts in concert with other factors. A class of ubiquitous environmental chemicals that are hypothesized to potentially function in this low-dose capacity are synthesized polybrominated diphenyl ethers (PBDEs). PBDEs can affect correlates of carcinogenesis that include genomic instability and inflammation. However, the effect of low-dose PBDE exposure on such correlates in mammary tissue has not been examined. In the present study, low-dose long-term (16 weeks) administration of PBDE to mice modulated transcriptomic indicators of genomic integrity and innate immunity in normal mammary tissue. PBDE increased transcriptome signatures for the Nuclear Factor Erythroid 2 Like 2 (NFE2L2) response to oxidative stress and decreased signatures for non-homologous end joining DNA repair (NHEJ). PBDE also decreased transcriptome signatures for the cyclic GMP-AMP Synthase - Stimulator of Interferon Genes (cGAS-STING) response, decreased indication of Interferon Stimulated Gene Factor 3 (ISGF3) and Nuclear Factor Kappa B (NF-κB) transcription factor activity, and increased digital cytometry estimates of immature dendritic cells (DCs) in mammary tissue. Replication of the PBDE exposure protocol in mice susceptible to mammary carcinogenesis resulted in greater tumor development. The results support the notion that ongoing exposure to low levels of PBDE can disrupt facets of genomic integrity and innate immunity in mammary tissue. Such effects affirm that synthesized PBDEs are a class of environmental chemicals that reasonably fit the low-dose mixture hypothesis. |
format | Online Article Text |
id | pubmed-9413140 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94131402022-08-27 Low-dose exposure to PBDE disrupts genomic integrity and innate immunity in mammary tissue Lamkin, Donald M. Chen, Shiuan Bradshaw, Karen P. Xu, Shili Faull, Kym F. Sloan, Erica K. Cole, Steve W. Front Genet Genetics The low-dose mixture hypothesis of carcinogenesis proposes that exposure to an environmental chemical that is not individually oncogenic may nonetheless be capable of enabling carcinogenesis when it acts in concert with other factors. A class of ubiquitous environmental chemicals that are hypothesized to potentially function in this low-dose capacity are synthesized polybrominated diphenyl ethers (PBDEs). PBDEs can affect correlates of carcinogenesis that include genomic instability and inflammation. However, the effect of low-dose PBDE exposure on such correlates in mammary tissue has not been examined. In the present study, low-dose long-term (16 weeks) administration of PBDE to mice modulated transcriptomic indicators of genomic integrity and innate immunity in normal mammary tissue. PBDE increased transcriptome signatures for the Nuclear Factor Erythroid 2 Like 2 (NFE2L2) response to oxidative stress and decreased signatures for non-homologous end joining DNA repair (NHEJ). PBDE also decreased transcriptome signatures for the cyclic GMP-AMP Synthase - Stimulator of Interferon Genes (cGAS-STING) response, decreased indication of Interferon Stimulated Gene Factor 3 (ISGF3) and Nuclear Factor Kappa B (NF-κB) transcription factor activity, and increased digital cytometry estimates of immature dendritic cells (DCs) in mammary tissue. Replication of the PBDE exposure protocol in mice susceptible to mammary carcinogenesis resulted in greater tumor development. The results support the notion that ongoing exposure to low levels of PBDE can disrupt facets of genomic integrity and innate immunity in mammary tissue. Such effects affirm that synthesized PBDEs are a class of environmental chemicals that reasonably fit the low-dose mixture hypothesis. Frontiers Media S.A. 2022-08-12 /pmc/articles/PMC9413140/ /pubmed/36035174 http://dx.doi.org/10.3389/fgene.2022.904607 Text en Copyright © 2022 Lamkin, Chen, Bradshaw, Xu, Faull, Sloan and Cole. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Lamkin, Donald M. Chen, Shiuan Bradshaw, Karen P. Xu, Shili Faull, Kym F. Sloan, Erica K. Cole, Steve W. Low-dose exposure to PBDE disrupts genomic integrity and innate immunity in mammary tissue |
title | Low-dose exposure to PBDE disrupts genomic integrity and innate immunity in mammary tissue |
title_full | Low-dose exposure to PBDE disrupts genomic integrity and innate immunity in mammary tissue |
title_fullStr | Low-dose exposure to PBDE disrupts genomic integrity and innate immunity in mammary tissue |
title_full_unstemmed | Low-dose exposure to PBDE disrupts genomic integrity and innate immunity in mammary tissue |
title_short | Low-dose exposure to PBDE disrupts genomic integrity and innate immunity in mammary tissue |
title_sort | low-dose exposure to pbde disrupts genomic integrity and innate immunity in mammary tissue |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9413140/ https://www.ncbi.nlm.nih.gov/pubmed/36035174 http://dx.doi.org/10.3389/fgene.2022.904607 |
work_keys_str_mv | AT lamkindonaldm lowdoseexposuretopbdedisruptsgenomicintegrityandinnateimmunityinmammarytissue AT chenshiuan lowdoseexposuretopbdedisruptsgenomicintegrityandinnateimmunityinmammarytissue AT bradshawkarenp lowdoseexposuretopbdedisruptsgenomicintegrityandinnateimmunityinmammarytissue AT xushili lowdoseexposuretopbdedisruptsgenomicintegrityandinnateimmunityinmammarytissue AT faullkymf lowdoseexposuretopbdedisruptsgenomicintegrityandinnateimmunityinmammarytissue AT sloanericak lowdoseexposuretopbdedisruptsgenomicintegrityandinnateimmunityinmammarytissue AT colestevew lowdoseexposuretopbdedisruptsgenomicintegrityandinnateimmunityinmammarytissue |