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  • 1
    ISSN: 1432-0738
    Keywords: PCDD mixtures ; Induction of P450IA1 ; 2,3,7,8-Cl4DD equivalents ; Human hepatoma HepG2 cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Dose-response curves of the induction of P4501A1-dependent 7-ethoxyresorufin O-deethylase (EROD) were analyzed in human hepatoma HepG2 cells treated with defined mixtures of polychlorinated dibenzop-dioxins (PCDDs) and their 2,3,7,8-substituted constituents, similar to previous studies with rat hepatocytes and H4IIE cells (Schrenk et al. 1991). PCDDs appear to act less potent in human HepG2 cells in comparison with rat cells. For example, EC50 values of 2,3,7,8-Cl4DD were 8-fold and 19-fold higher than in rat H4IIE cells and hepatocytes, respectively. EC50 values of PCDDs were compared with that of 2,3,7,8-Cl4DD and expressed as 2,3,7,8-Cl4DD equivalents (TEs). Although the rank order of PCDD potencies was similar, TEs for some PCDDs (1,2,3,7,8-Cl5 DD; TE=0.75 and 1,2,3,4,7,8-Cl6DD; TE=0.61) were found to be higher than in the rat system. In contrast to rat cells no significant induction of EROD could be detected with Cl8DD in HepG2 cells up to its limit of solubility. Experimentally determined TEs of PCDD mixtures containing 49 constituents were found to be largely due to additive effects of their 2,3,7,8-substituted constituents.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0738
    Keywords: PCDD mixtures ; Induction of P450IA1 ; 2,3,7,8-Cl4DD equivalents ; H4IIE cells ; Primary cultures of rat hepatocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract As a first step to assess biological activities of complex mixtures of polychlorinated dibenzo-p-dioxins (PCDDs), induction of 7-ethoxyresorufin O-deethylase (EROD) by defined mixtures and their constituents has been analysed in vitro. Two cell systems have been compared: primary hepatocyte cultures and hepatoma H4IIE cells. EC50 values of PCDDs were compared with that of the most potent compound, 2,3,7,8-Cl4DD (2,3,7,8-tetrachlorodibenzo-p-dioxin) and expressed as 2,3,7,8-Cl4DD equivalents (TEs). TEs for three defined mixtures containing up to 49 PCDDs could be predicted from the sum of TEs for the 2,3,7,8-substituted congeners. Efficacies (maximal enzyme induction) of less potent PCDDs (1,2,3,4-Cl4DD, Cl8DD and of a mixture containing 86% Cl8DD and of benz(a)anthracene were lower in hepatocytes (by 33%) and in H4IIE cells (by 50%). The results suggest that biological activities of complex PCDD mixtures are largely due to additive effects of their 2,3,7,8-substituted consituents.
    Type of Medium: Electronic Resource
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