Relative potencies of individual polycyclic aromatic hydrocarbons to induce dioxinlike and estrogenic responses in three cell lines.
The dioxinlike and estrogenic relative potencies (REPs) of 16 priority polycyclic aromatic hydrocarbons (PAHs), seven methylated PAHs, and two hydroxylated PAHs were examined using three in vitro cell bioassays. An in vitro ethoxyresorufin-O-deethylase assay with PLHC-1 fish hepatoma cells and in vitro luciferase assay with H4IIE-luc recombinant rat hepatoma cells were used to evaluate dioxinlike potency. An in vitro luciferase assay with MVLN, recombinant human breast carcinoma cells, was used to evaluate estrogenic potency. Seven of the 16 priority PAHs tested induced significant dioxinlike responses. Excluding outliers with large ranges of uncertainty, the dioxinlike REPs for the PAHs ranged from 10(-6) to 10(-3). This is similar to the REPs reported for other xenobiotics of concern including polychlorinated naphthalenes (PCNs) and some polychlorinated biphenyls (PCBs). In general, REP estimates generated in this study were similar to those reported previously. However, a comparison of the estimates of total 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents derived using assay-specific REPs with REPs reported in other studies indicated that the use of nonspecific REPs could lead to significant error in mass-balance (potency-balance) analyses. A 10-h acid treatment completely destroyed the dioxinlike activity of a PAH mixture. Among the compounds tested, only benzo[a]anthracene and dibenz[a,h]anthracene induced significant responses in the MVLN bioassay. Relative estrogenic potencies were estimated to be approximately 10(-7). Overall, this research contributes to the growing consensus regarding the dioxinlike potency of priority PAHs and PAH derivatives and provides some additional evidence about potentially estrogenic PAHs.
Villeneuve
D L
DL
Department of Zoology, National Food Safety and Toxicology Center, Institute for Environmental Toxicology, Michigan State University, East Lansing, Michigan 48824, USA. villene1@msu.edu
Khim
J S
JS
Kannan
K
K
Giesy
J P
JP
D000818:Animals; D001681:Biological Assay; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D003530:Cyprinidae; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D004147:Dioxins / Q000009:adverse effects* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D011084:Polycyclic Aromatic Hydrocarbons / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D051381:Rats; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000502:physiology; D012016:Reference Values; D014407:Tumor Cells, Cultured
D004147:Dioxins; D011084:Polycyclic Aromatic Hydrocarbons; D011960:Receptors, Estrogen; D019363:Cytochrome P-450 CYP1A1