Induction of aryl hydrocarbon hydroxylase AHH by two previously uncharacterized pentachlorinated biphenyls in a mouse and a rat hepatoma cell line

Abstract

Induction of aryl hydrocarbon hydroxylase (AHH) activity in a mouse (Hepa-1) and a rat (H4IIE) hepatoma cell line was used as an indicator of biological effect of two coplanar polychlorinated biphenyls of different types. The previously uncharacterized pentachlorinated biphenyls used were non- ortho substituted 3,3′,4,5,5′-PeCB (PCB 127) and mono- ortho substituted 2,3,3′,4,5′-PeCB (PCB 108). In Hepa-1 cells, 50 μM 3,3′,4,5,5′-PeCB caused nearly the same induction of AHH as 1 nM 2,3,7,8-TCDD (TCDD). It should be noted, however, that there was a 50,000-fold difference in the effective concentrations. 2,3,3′,4,5′-PeCB was a much weaker inducer of AHH. As 50 μM concentration 2,3,3′,4,5′-PeCB was cytotoxic to Hepa-1 cells, whereas 3,3′,4,5,5′-PeCB was not. This supports some earlier observations that AHH induction and general cytotoxicity do not always coincide. In H4IIE, neither of the PeCBs was cytotoxic in the concentrations studied. However, both PeCBs were AHH inducers. The different response of the two cell lines studied implies that for the estimation of “TCDD equivalents” more than one cell line should be studied. According to ED50-values (about 10 pM for Hepa-1; about 15 pM for H4IIE) obtained from the dose-response curves, Hepa-1 was somewhat more responsive than H4IIE to TCDD.