Heterocyclic aromatic hydrocarbons show estrogenic activity upon metabolization in a recombinant transactivation assay.
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.
Institute for Environmental Research, Department of Ecosystem Analysis, ABBt-Aachen Biology and Biotechnology, RWTH Aachen University , Worringerweg 1, 52074 Aachen, Germany.
Markus
M
Brinkmann
Sibylle
S
Maletz
Martin
M
Krauss
Kerstin
K
Bluhm
Sabrina
S
Schiwy
Jochen
J
Kuckelkorn
Andreas
A
Tiehm
Werner
W
Brack
Henner
H
Hollert
D001681:Biological Assay / Q000379:methods*; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D016001:Confidence Intervals; D004967:Estrogens / Q000378:metabolism*; D006801:Humans; D011084:Polycyclic Aromatic Hydrocarbons / Q000378:metabolism*; D021281:Quantitative Structure-Activity Relationship; D011960:Receptors, Estrogen / Q000378:metabolism; D011995:Recombination, Genetic; D053719:Tandem Mass Spectrometry; D015533:Transcriptional Activation; D014867:Water
D004967:Estrogens; D011084:Polycyclic Aromatic Hydrocarbons; D011960:Receptors, Estrogen; D014867:Water