The TEF system for
dioxin-like compounds has included assignment of TEF values for mono-ortho
polychlorinated biphenyls (MO-
PCBs). Small traces of
aryl hydrocarbon receptor (AhR)-active impurities could result in artifactually higher relative potency (REP) values. MO-
PCBs -105, -118, -156, and -167 were purified on an active
charcoal column to remove AhR agonists that could be present as impurities. Activation or inhibition of AhR-dependent gene expression by purified MO-
PCBs was studied in stably transfected cell lines (H1G1.1c3 mouse, H4G1.1c2 rat
hepatoma), containing an AhR-responsive (AhR-EGFP) reporter gene. In addition,
EROD activity was used as marker for
CYP1A1 activity in these cell lines. MO-
PCBs -105, -118, -156 induced AhR-EGFP expression in both rodent cell lines, with
PCB-156 (10microM) being most effectively; inducing gene expression to approximately 27% of
TCDD (mouse cells) and 62.5+/-3.4% (rat cells) of
TCDD. This concurred with increased
EROD activity in both cell lines to maxima of 20.5+/-1.5% and 68+/-3.2% of
TCDD, respectively. No induction was observed for PCB-167. In the H1G1.1c3 mouse cells,
PCB-105, -118 and -156 (10microM) significantly reduced
TCDD-induced AhR-EGFP expression to 50.9+/-2.9%, 58.3+/-2.2% and 70.8+/-1.3% of
TCDD. Reduced
EROD activity was also observed, of 39.3+/-2.8%, 67+/-5% and 48.3+/-4% compared to
TCDD. PCB-167 did not result in significant reduction. In rat cells, only
PCB-156 resulted in significant decrease in
TCDD-induced AhR-EGFP expression of 35%, suggesting species differences play a role. Our results suggest that purification of MO-
PCBs is an essential step in determining accurate REP values, and could very likely lead to lower TEF values than those presently assigned by the WHO.