title: Relative potencies of polychlorinated dibenzo-p-dioxin, dibenzofuran, and biphenyl congeners to induce cytochrome P4501A mRNA in a zebrafish liver cell line.
abstract: Induction of cytochrome P4501A (CYP1A) mRNA by polychlorinated dibenzo-p-dioxin (PCDD), polychlorinated dibenzofuran (PCDF), and polychlorinated biphenyl (PCB) congeners was measured in a zebrafish liver (ZF-L) cell line. The ZF-L cells were far less sensitive to PCDD, PCDF, and PCB congeners than were other fish cell lines. The 2,3,7,8-PCDDs, 2,3,7,8-PCDFs, and PCB 126 caused dose-related induction. All other PCBs tested, including other coplanar as well as ortho-substituted congeners, were ineffective at inducing CYP1A. The potency of each congener that gave a response, relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin, was determined. The ZF-L cell-derived relative potency values (REPs) are similar to other in vitro REPs in that the ZF-L cell-derived REPs are generally higher than those derived from in vivo models. Furthermore, the ZF-L cell-derived REPs are generally within fivefold of REPs determined in a variety of rainbow trout systems when the same endpoint in the same tissue are compared. Analysis of these data indicates that REPs based on molecular and biochemical responses in sensitive and insensitive species are similar, but overestimate relative in vivo toxicity in the rainbow trout. The ZF-L cell-derived REPs expand the database of REPs, providing additional information that will be useful in quantifying the uncertainty associated with applying consensus fish-specific toxic equivalency factors in ecological risk assessment.
authors.affiliation: U.S. Environmental Protection Agency, National Health and Environmental Effects Research Laboratory, 6201 Congdon Boulevard, Duluth, Minnesota 55804, USA. henry.tala@epa.gov
authors.forename: T R
authors.initials: TR
authors.lastname: Henry
authors.forename: D J
authors.initials: DJ
authors.lastname: Nesbit
authors.forename: W
authors.initials: W
authors.lastname: Heideman
authors.forename: R E
authors.initials: RE
authors.lastname: Peterson
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000633:toxicity*; D002460:Cell Line; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004147:Dioxins / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics*; D015027:Zebrafish
chemical_list: D001572:Benzofurans; D004147:Dioxins; D012333:RNA, Messenger; C023614:dibenzofuran; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls