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Transcriptional Responses as Biomarkers of General Toxicity : A Systematic Review and Meta-Analysis on Metal-Exposed Bivalves

Ekelund Ugge, Gustaf M O LU orcid ; Sahlin, Ullrika LU ; Jonsson, Annie and Berglund, Olof LU (2023) In Environmental Toxicology and Chemistry 42(3). p.628-641
Abstract

Through a systematic review and a series of meta-analyses, we evaluated the general responsiveness of putative transcriptional biomarkers of general toxicity and chemical stress. We targeted metal exposures performed on bivalves under controlled laboratory conditions, and selected six transcripts associated with general toxicity for evaluation: catalase (cat), glutathione-S-transferase (gst), heat shock proteins 70 and 90 (hsp70, hsp90), metallothionein (mt) and superoxide dismutase (sod). Transcriptional responses (n = 396) were extracted from published scientific articles (k = 22) and converted to log response ratios (lnRRs). By estimating toxic units (TUs), we normalized different metal exposures to a common scale, as a proxy of... (More)

Through a systematic review and a series of meta-analyses, we evaluated the general responsiveness of putative transcriptional biomarkers of general toxicity and chemical stress. We targeted metal exposures performed on bivalves under controlled laboratory conditions, and selected six transcripts associated with general toxicity for evaluation: catalase (cat), glutathione-S-transferase (gst), heat shock proteins 70 and 90 (hsp70, hsp90), metallothionein (mt) and superoxide dismutase (sod). Transcriptional responses (n = 396) were extracted from published scientific articles (k = 22) and converted to log response ratios (lnRRs). By estimating toxic units (TUs), we normalized different metal exposures to a common scale, as a proxy of concentration. Using Bayesian hierarchical random effect models, we then tested the effects of metal exposure on lnRR, both for metal exposure in general and in meta-regressions using TU and exposure time as independent variables. Corresponding analyses were also repeated with transcript and tissue as additional moderators. Observed patterns were similar for general as for transcript- and tissue-specific responses. The expected overall response to arbitrary metal exposure was a lnRR of 0.50, corresponding to a 65 % increase relative a non-exposed control. However, when accounting for publication bias, the estimated 'true' response showed no such effect. Furthermore, expected response magnitude increased slightly with exposure time, but there was little support for general monotonic concentration-dependence with regards to TU. Altogether, this work reveals potential limitations that need consideration prior to applying the selected transcripts as biomarkers in environmental risk assessment. This article is protected by copyright. All rights reserved. Environ Toxicol Chem 2022;00:0-0. © 2022 SETAC.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Environmental Toxicology and Chemistry
volume
42
issue
3
pages
628 - 641
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:85142195831
  • pmid:36200657
ISSN
0730-7268
DOI
10.1002/etc.5494
project
Transcriptional biomarkers of toxicity - powerful tools or random noise? An applied perspective from studies on bivalves
language
English
LU publication?
yes
additional info
This article is protected by copyright. All rights reserved.
id
daf12cce-64e1-4a6a-aa49-7d682b1d18a1
date added to LUP
2022-11-23 08:30:51
date last changed
2024-04-15 19:39:40
@article{daf12cce-64e1-4a6a-aa49-7d682b1d18a1,
  abstract     = {{<p>Through a systematic review and a series of meta-analyses, we evaluated the general responsiveness of putative transcriptional biomarkers of general toxicity and chemical stress. We targeted metal exposures performed on bivalves under controlled laboratory conditions, and selected six transcripts associated with general toxicity for evaluation: catalase (cat), glutathione-S-transferase (gst), heat shock proteins 70 and 90 (hsp70, hsp90), metallothionein (mt) and superoxide dismutase (sod). Transcriptional responses (n = 396) were extracted from published scientific articles (k = 22) and converted to log response ratios (lnRRs). By estimating toxic units (TUs), we normalized different metal exposures to a common scale, as a proxy of concentration. Using Bayesian hierarchical random effect models, we then tested the effects of metal exposure on lnRR, both for metal exposure in general and in meta-regressions using TU and exposure time as independent variables. Corresponding analyses were also repeated with transcript and tissue as additional moderators. Observed patterns were similar for general as for transcript- and tissue-specific responses. The expected overall response to arbitrary metal exposure was a lnRR of 0.50, corresponding to a 65 % increase relative a non-exposed control. However, when accounting for publication bias, the estimated 'true' response showed no such effect. Furthermore, expected response magnitude increased slightly with exposure time, but there was little support for general monotonic concentration-dependence with regards to TU. Altogether, this work reveals potential limitations that need consideration prior to applying the selected transcripts as biomarkers in environmental risk assessment. This article is protected by copyright. All rights reserved. Environ Toxicol Chem 2022;00:0-0. © 2022 SETAC.</p>}},
  author       = {{Ekelund Ugge, Gustaf M O and Sahlin, Ullrika and Jonsson, Annie and Berglund, Olof}},
  issn         = {{0730-7268}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{628--641}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Environmental Toxicology and Chemistry}},
  title        = {{Transcriptional Responses as Biomarkers of General Toxicity : A Systematic Review and Meta-Analysis on Metal-Exposed Bivalves}},
  url          = {{http://dx.doi.org/10.1002/etc.5494}},
  doi          = {{10.1002/etc.5494}},
  volume       = {{42}},
  year         = {{2023}},
}