2,4‐Dinitrophenol induces apoptosis in As4.1 juxtaglomerular cells through rapid depletion of GSH

et al. 2021

Preprint

Pesticides are critical for invasive species management, but often have negative effects on non-target native biota. Tolerance to pesticides should have an evolutionary basis, but this is poorly understood. Invasive sea lamprey (Petromyzon marinus) populations in North America have been controlled with a pesticide lethal to them at lower concentrations than native fishes. We addressed how interspecific variation in gene expression and detoxification gene diversity confer differential pesticide sensitivity in two fish species. We exposed sea lamprey and bluegill (Lepomis macrochirus), a tolerant native species, to TFM, a pesticide commonly used in sea lamprey control, and used whole-transcriptome sequencing of gill and liver to characterize the cellular response. Comparatively, bluegill exhibited a larger number of detoxification genes expressed and a larger number of responsive transcripts overall, which likely contributes to greater tolerance to TFM. Understanding the genetic and physiological basis for pesticide tolerance is crucial for managing invasive species.

Section: Discussionsupporting

confidence: 55%

Variation in the transcriptome response and detoxification gene diversity drives pesticide tolerance in fishes

et al. 2021

Preprint

“…52 While TFM effects on ROS generation have not been quantified, TFM does increase mitochondrial respiration rates, 18 which may serve to elevate cellular ROS levels. 53 Coupled with the GO term enrichment patterns, our results suggest that TFM-induced ROS is likely mediating cellular arrest as seen in niclosamide 54,55 and 2,4-dinitrophenol (DNP, a TFM analogue) 56,57 exposures. While fish-specific examples are limited, zebrafish (D. rerio) exposed to 4-nitrophenol experienced reduced cellular growth and proliferation and heightened cell death, 52 aligning with our results.…”

Section: ■ Discussionmentioning

confidence: 55%

Variation in the Transcriptome Response and Detoxification Gene Diversity Drives Pesticide Tolerance in Fishes

et al. 2022

Environ. Sci. Technol.

Pesticides are critical for invasive species management but often have negative effects on nontarget native biota. Tolerance to pesticides should have an evolutionary basis, but this is poorly understood. Invasive sea lamprey (Petromyzon marinus) populations in North America have been controlled with a pesticide lethal to them at lower concentrations than native fishes. We addressed how interspecific variation in gene expression and detoxification gene diversity confer differential pesticide sensitivity in two fish species. We exposed sea lamprey and bluegill (Lepomis macrochirus), a tolerant native species, to 3-trifluoromethyl-4-nitrophenol (TFM), a pesticide commonly used in sea lamprey control. We then used whole-transcriptome sequencing of gill and liver to characterize the cellular response in both species. Comparatively, bluegill exhibited a larger number of detoxification genes expressed and a larger number of responsive transcripts overall, which likely contributes to greater tolerance to TFM. Understanding the genetic and physiological basis for pesticide tolerance is crucial for managing invasive species.

“…While these are the first transcriptomic data examining niclosamide-TFM interactions in a teleost, our results align with the effects of these toxicants on their own. For example, both niclosamide (Jin et al, 2010;Liu et al, 2015;Wieland et al, 2013) and other phenolic compounds similar to TFM, notably 2,4-dinitrophenol (Han et al, 2008a;Han et al, 2008b;Lam et al, 2013;Miyoshi et al, 2006), are capable of arresting the cell cycle, limiting cellular proliferation, and enhancing apoptosis in a clinical setting. In fishes, TFM itself has been shown to enrich GO terms related to cell death and arrested growth in both bluegill and sea lamprey (Lawrence and Grayson et al 2022).…”

Section: The Associated Toxicological Impacts Of a Tfm:niclosamide Mi...mentioning

confidence: 99%

Transcriptomic impacts and potential routes of detoxification in a lampricide-tolerant teleost exposed to TFM and niclosamide

et al. 2023

Preprint

Sea lamprey (Petromyzon marinus) control in the Laurentian Great Lakes of North America often relies on the application of 3-trifluoromethyl-4-nitrophenol (TFM) and niclosamide mixtures to kill larval sea lamprey. Selectivity of TFM against lampreys appears to be due to differential detoxification ability in these jawless fishes compared to bony fishes, particularly teleosts. However, the proximate mechanisms of tolerance to the TFM and niclosamide mixture and the mechanisms of niclosamide toxicity on its own are poorly understood, especially among non-target fishes. Here, we used RNA sequencing to identify specific mRNA transcripts and functional processes that responded to niclosamide or a TFM:niclosamide mixture in bluegill (Lepomis macrochirus). Bluegill were exposed to niclosamide or TFM:niclosamide mixture, along with a time-matched control group, and gill and liver tissues were sampled at 6, 12, and 24 h. We summarized the whole-transcriptome patterns through gene ontology (GO) term enrichment and through differential expression of detoxification genes. The niclosamide treatment resulted in an upregulation of several transcripts associated with detoxification (cyp, ugt, sult, gst), which may help explain the relatively high detoxification capacity in bluegill. Conversely, the TFM:niclosamide mixture resulted in an enrichment of processes related to arrested cell cycle and growth, and cell death alongside a diverse detoxification gene response. Detoxification of both lampricides likely involves the use of phase I and II biotransformation genes. Our findings strongly suggest that the unusually high tolerance of bluegill to lampricides is due to these animals having an inherently high capacity and flexible detoxification response to such compounds.