Estrogenic/Antiestrogenic Activities of Polycyclic Aromatic Hydrocarbons and Their Monohydroxylated Derivatives by Yeast Two-Hybrid Assay

Abstract

Estrogenic/antiestrogenic activities of 14 polycyclic aromatic hydrocarbons (PAHs) and 63 monohydroxylated PAHs (OHPAHs) having 2 to 6 rings were evaluated by yeast two-hybrid assay expressing human estrogen receptor α. Relative effective potencies of estrogenic and antiestrogenic activities were calculated as the inverse values of the relative concentration of the test compound that gave the same activities of E 2 and 4-hydroxytamoxifen, respectively. PAHs did not show any estrogenic/antiestrogenic activity, but several OHPAHs having 3 to 5 rings showed activities. Especially, OHPAHs having 4 rings such as 3-, 4-and 10-hydroxybenz[a]anthracenes (3-, 4-and 10-OHBaAs) and 2-hydroxychrysene (2-OHCh) showed strongly estrogenic activity. Several other OHPAHs having 4 rings such as 2-and 3-hydroxybenzo[c]phenanthrenes (2-, 3-OHBcPhs), 2-OHBaA and 3-OHCh showed strongly antiestrogenic activity. The length-to-breadth (L/B) ratios of the rectangular van der Walls planes surrounding the ring molecules of estrogenic OHPAHs were in the narrow range from 1.599 to 1.734. The distances between the oxygen atom of the phenol group and farthest hydrogen atom (O-H distance) of the estrogenic OHPAHs ranged from 10.825 Å to 11.738 Å. The L/B ratios and O-H distances of antiestrogenic OHPAHs were in the wider ranges from 1.277 to 1.734 and from 8.47 Å to 11.681 Å, respectively. The partial charges (atomic unit) of the phenol group of both estrogenic and antiestrogenic OHPAHs were in the range from −0.250 atmic unit (au) to −0.253 au. The similarity of these values to those of E 2 and diethylstilbestrol suggested that the compositions of estrogenic OHPAHs were similar to them and that the compositional conditions of estrogenic OHPAHs were much smaller than those of antiestrogenic OHPAHs. These results raise the possibility of predicting the estrogenic/antiestrogenic activities of OHPAHs from their structural characteristics, although using only the above three parameters might not be enough for accurate estimations.

Screening of multiple hormonal activities in surface water and sediment from the Pearl River system, South China, using effect‐directed in vitro bioassays

“…The fungicide vinclozolin exhibits antiandrogenic activity in rats [22], and some pesticides (e.g., p,p 0 -1,1-dichloro-2,2-bis[pchorophenyl]ethylene [p,p 0 -DDE] and linuron) also show antiandrogenic activities [18]. Furthermore, some pollutants, such as polycyclic aromatic hydrocarbons, in the environment can act as both agonist and antagonist of estrogen or androgen receptors [15,23]. Hence, EDCs are often a complex mixture in environmental matrices and display hormonal effects through multiple action modes on hormone receptors.…”

Environmental Behaviors and Toxicities of Polycyclic Aromatic Hydrocarbons and Nitropolycyclic Aromatic Hydrocarbons

“…[4][5][6] These oxidative metabolites also produce reactive oxygen species. 7,8) It is important to estimate not only the carcinogenicity/mutagenicity but also activities of endocrine disruption and production of reactive oxygen species of PAHs and NPAHs from the view point of toxicity markers of PM 2.5 .…”

Benzo[c]fluorene in Urban Air: HPLC Determination and Mutagenic Contribution Relative to Benzo[a]pyrene

“…[4][5][6] Many PAHs and NPAHs exhibit carcinogenic, mutagenic, 7,8 or endocrine-disrupting activity. 9 Benzo[a]pyrene (BaP), for example, is classified as a Group 1 compound (carcinogenic to humans) by the International Agency for Research on Cancer and is used as an indicator of environmental pollution. [10][11][12] The PAHs dibenzo[a,l]pyrene (DBalP) and benz[ j ]-aceanthrylene (BjAC) were recently classified as Group 2A (probably carcinogenic to humans) and Group 2B (possibly carcinogenic to humans) compounds, respectively.…”