Heterocyclic Aromatic Hydrocarbons Show Estrogenic Activity upon Metabolization in a Recombinant Transactivation Assay

Abstract

Heterocyclic aromatic hydrocarbons (hetero-PAHs) are increasingly studied at contaminated sites; especially at former industrial facilities where coal tar-oil was handled, e.g., wood treatment plants, high concentrations of hetero-PAHs are frequently detected in groundwater plumes. In previous studies, fractions of groundwater with high estrogenic activity contained hetero-PAHs and their hydroxylated metabolites. To evaluate this preliminary evidence, selected hetero-PAHs were screened for their estrogenic activity in lyticase yeast estrogen screen (LYES) and ER CALUX. All tested substances were inactive in the LYES. Hetero-PAHs such as acridine, xanthene, indole, 2-methylbenzofuran, 2,3-dimethylbenzofuran, dibenzofuran, dibenzothiophene, quinoline, and 6-methylquinoline were positive in the ER CALUX, with estradiol equivalence factors (EEFs) from 2.85 × 10(-7) to 3.18 × 10(-5). The EEF values of these substances were comparable to those of other xenoestrogens (e.g., alkylphenols or bisphenol A) that are sometimes found in surface water. Chemical analyses revealed that T47Dluc cells could metabolize most of the substances. Among the metabolites (tentatively) identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) were hydroxides and their keto tautomers, sulfates, sulfoxides, and N-oxides. Because of their high concentrations measured in groundwater, we conclude that hetero-PAHs and metabolites may be a potential risk and should be the subject of further research.

Methylated polycyclic aromatic hydrocarbons and/or their metabolites are important contributors to the overall estrogenic activity of polycyclic aromatic hydrocarbon–contaminated soils

“…The REP values in the present study were 2‐fold higher than those in other studies except for the REP value of benzo[ a ]pyrene, which was 10‐fold higher. However, results for the heterocyclic compounds quinoline and dibenzothiophene differed significantly, and although the compounds were not potent inducers in the VM7Luc4E2‐TA, REP values could be determined in the ER‐CALUX bioassay . The MCF‐7 and vMCF‐7 cell lines are genetically similar , which may explain the similarity in REP values of the MVLN assay and the VM7luc4E2 TA.…”

Identification and Toxicological Evaluation of Unsubstituted PAHs and Novel PAH Derivatives in Pavement Sealcoat Products

“…Heterocylic-PAHs (Hetero-PAHs) are a group of PAH derivatives where one of the carbons within the ring system is replaced by nitrogen, oxygen, or sulfur. Recent research has indicated that some Hetero-PAHs show estrogenic activity 16 and ecotoxicity. 17 Nitro-PAHs (NPAHs) and oxygenated-PAHs (OPAHs) have been detected in the environment 18–20 and some are classified as known mutagens and/or possible or probable human carcinogens (group A2 or B2, respectively).…”

Aerobic Bioremediation of PAH Contaminated Soil Results in Increased Genotoxicity and Developmental Toxicity

“…12–16 Heterocyclic PAHs, HPAHs (PAH derivatives containing heteroatoms oxygen, nitrogen, or sulphur), have been shown to contribute significantly to toxicity at contaminated sites, and their metabolites have been linked to endocrine disruption. 17,18 …”