In vitro induction of CYP1A1‐associated activities in human and rodent cell lines by commercial and tissue‐extracted halogenated aromatic hydrocarbons

Abstract

AbstractDespite reports of species‐specific differences, the rat cell line H4IIE continues to be used to assess the toxicity of many halogenated aromatic hydrocarbon (HAH) contaminants for diverse populations using an approach that relates aryl hydrocarbon (Ah) receptor‐mediated responses by HAHs to that of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD). To assess the relevance of H4IIE for human populations, we examined levels of aryl hydrocarbon hydroxylase (AHH) and ethyoxyresorufin O‐deethylase (EROD) activities in H4IIE rat liver, HepG2 human liver, and MCF‐7 human breast cells treated with TCDD and three coplanar polychlorinated biphenyl (PCB) congeners (77, 126, 169), alone or in combination, and to fractions extracted from the muscle tissue of Lake Ontario rainbow trout (Oncorhynchus mykiss). H4IIE was generally more sensitive to all HAH treatments. Both AHH and EROD activities were induced in all cells treated with TCDD and PCB‐126, alone or combined with each other. In contrast, neither activity was induced in human cells treated with PCB‐77 or PCB‐169. For inducing concentrations of PCBs, the induction response in all cell lines treated with 5 nM TCDD‐PCB mixtures was generally nonadditive; only the response in H4IIE treated with 10−3 nM TCDD–PCB mixtures was generally additive. With tissue extracts, induction was restricted to H4IIE cells treated with TCDD/PCB‐or organochloride pesticide‐containing fractions. Our initial results suggest that differences in the properties of each HAH or in levels of Ah receptor in each cell line are not likely to underlie the significant differences in the murine/human induction responses.