Ekelund Ugge Gustaf M O, Sahlin Ullrika, Jonsson Annie, Berglund Olof
Department of Biology, Lund University, Lund, Sweden.
School of Bioscience, University of Skövde, Skövde, Sweden.
Environ Toxicol Chem. 2023 Mar;42(3):628-641. doi: 10.1002/etc.5494. Epub 2023 Feb 10.
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, glutathione-S-transferase, heat shock proteins 70 and 90, metallothionein, and superoxide dismutase. Transcriptional responses (n = 396) were extracted from published scientific articles (k = 22) and converted to log response ratios (lnRRs). By estimating toxic units, 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 toxic unit and exposure time as independent variables. Corresponding analyses were also repeated with transcript and tissue as additional moderators. Observed patterns were similar for general and for transcript- and tissue-specific responses. The expected overall response to arbitrary metal exposure was an lnRR of 0.50, corresponding to a 65% increase relative to a nonexposed 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 regard to toxic unit. Altogether, the present study reveals potential limitations that need consideration prior to applying the selected transcripts as biomarkers in environmental risk assessment. Environ Toxicol Chem 2023;42:628-641. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
通过系统综述和一系列荟萃分析，我们评估了一般毒性和化学应激假定转录生物标志物的总体反应性。我们针对在受控实验室条件下对双壳贝类进行的金属暴露，并选择了六个与一般毒性相关的转录本进行评估：过氧化氢酶、谷胱甘肽 - S - 转移酶、热休克蛋白70和90、金属硫蛋白以及超氧化物歧化酶。从已发表的科学文章（k = 22）中提取转录反应（n = 396），并将其转换为对数反应比（lnRRs）。通过估计毒性单位，我们将不同的金属暴露归一化为一个共同的尺度，作为浓度的替代指标。然后，我们使用贝叶斯分层随机效应模型，测试了金属暴露对lnRR的影响，包括一般金属暴露以及以毒性单位和暴露时间作为自变量的元回归分析。还以转录本和组织作为额外的调节变量重复了相应分析。一般反应以及转录本和组织特异性反应的观察模式相似。对任意金属暴露的预期总体反应是lnRR为0.50，相对于未暴露对照增加65%。然而，在考虑发表偏倚时，估计的“真实”反应并未显示出这种效应。此外，预期反应幅度随暴露时间略有增加，但对于毒性单位而言，几乎没有证据支持一般的单调浓度依赖性。总之，本研究揭示了在将选定的转录本用作环境风险评估中的生物标志物之前需要考虑的潜在局限性。《环境毒理学与化学》2023年；42：628 - 641。© 2022作者。由Wiley Periodicals LLC代表SETAC出版的《环境毒理学与化学》。
