Effects of Alkylation on Potency of Benz[a]anthracene for AhR2 Transactivation in Nine Species of Freshwater Fish

Abstract

Polycyclic aromatic hydrocarbons (PAHs) are naturally occurring or anthropogenic organic chemicals that can activate the aryl hydrocarbon receptor 2 (AhR2) and induce toxicity in fishes. Alkyl PAHs are more abundant than nonalkylated PAHs in certain environmental matrices and there is growing evidence that alkylation can increase potency, dependent on the position of alkylation. However, it is unknown if the effect of alkylation on potency is conserved across species. In addition, relatively little is known regarding the extent of interspecies variation in sensitivity to PAHs and alkyl PAHs. Therefore, objectives of the present study were to characterize potency of benz[a]anthracene (BAA) and three alkylated homologues representing different alkylation positions in nine phylogenetically diverse species of fish using a standardized in vitro AhR2 transactivation assay. BAA and each alkylated homologue activated the AhR2 in a concentrationdependent manner in each species. Position-dependent effects on potency were observed in every species, but these effects were not consistent across species. Interspecies variation in sensitivity to AhR2 activation by each PAH was observed and ranged by up to 561-fold. Alkylation both increased and decreased the range of interspecies variation and sensitivity, but the potency of each alkylated homologue relative to BAA ranged by less than an order of magnitude among species. These results represent an early step toward the consideration of alkylated homologues for more objective ecological risk assessments of PAHs to native fishes.

Assessing the Toxicity of Benzotriazole Ultraviolet Stabilizers to Fishes: Insights into Aryl Hydrocarbon Receptor-Mediated Effects

“…67−69 In fishes, interspecies differences in sensitivities to activation of the AhR2 can span several orders of magnitude between the most sensitive and least-sensitive species. 38,58 Specifically, TCDD and other chlorinated dioxin-like compounds show clear differences in species sensitivities to AhR2 activation and associated early life toxicities, with the zebrafish AhR2 being among the least sensitive to activation by TCDD. 38,70 As such, it is likely that zebrafish do not provide the optimal representation of sensitivities for native species of environmental and regulatory concern.…”

“…In fishes, interspecies differences in sensitivities to activation of the AhR2 can span several orders of magnitude between the most sensitive and least-sensitive species. , Specifically, TCDD and other chlorinated dioxin-like compounds show clear differences in species sensitivities to AhR2 activation and associated early life toxicities, with the zebrafish AhR2 being among the least sensitive to activation by TCDD. , As such, it is likely that zebrafish do not provide the optimal representation of sensitivities for native species of environmental and regulatory concern. Therefore, activation of the AhR2 of Japanese medaka, another model species, and seven native fish species, brook trout, fathead minnow, lake sturgeon, lake trout, northern pike, white sucker, and white sturgeon, by UV-P, UV-9, and UV-090 was determined in the in vitro AhR transactivation assay.…”

“…Statistical analysis for in vitro AhR activation was performed in R v.4.2.2 (The R Foundation for Statistical Computing, 2022) coupled to RStudio v.2022.12.0.353 (Rstudio Team 2022) as described in Dubiel et al Outliers were determined by preforming a Chi-squared test (statistical cutoff: p ≤ 0.05) using the Tests for Outliers package and then removed from the finalized data set . Dose–response curves were generated in Rstudio and fit using a four-parameter log–logistic function using the Analysis of Dose–response Curves package, and effective concentration threshold (EC threshold ) of activation of the AhR2 in COS-7 cells was established.…”