Low-dose exposure to PBDE disrupts genomic integrity and innate immunity in mammary tissue.

Autor:	Lamkin DM; Norman Cousins Center for PNI, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, United States.; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States.; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, United States., Chen S; Department of Cancer Biology, Beckman Research Institute of City of Hope, Duarte, CA, United States., Bradshaw KP; Norman Cousins Center for PNI, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, United States.; Department of Neuroscience, Stanford University School of Medicine, Stanford, CA, United States., Xu S; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, United States.; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States.; Crump Institute for Molecular Imaging, University of California, Los Angeles, Los Angeles, CA, United States., Faull KF; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States.; Pasarow Mass Spectrometry Laboratory, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, United States., Sloan EK; Norman Cousins Center for PNI, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, United States.; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, United States.; Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.; Division of Cancer Surgery, Peter MacCallum Cancer Centre-Victorian Comprehensive Cancer Centre, Melbourne, VIC, Austalia., Cole SW; Norman Cousins Center for PNI, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, United States.; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States.; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, United States.; Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in genetics [Front Genet] 2022 Aug 12; Vol. 13, pp. 904607. Date of Electronic Publication: 2022 Aug 12 (Print Publication: 2022).
DOI:	10.3389/fgene.2022.904607
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Lamkin, Chen, Bradshaw, Xu, Faull, Sloan and Cole.)
Databáze:	MEDLINE
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