Lipp H P, Schrenk D, Wiesmüller T, Hagenmaier H, Bock K W
Institute of Toxicology, University of Tübingen, Federal Republic of Germany.
Arch Toxicol. 1992;66(3):220-3. doi: 10.1007/BF01974019.
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 dibenzo-p-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-Cl5DD; TE = 0.75 and 1,2,3,7,8-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.
在用多氯代二苯并 - 对 - 二噁英（PCDDs）及其2,3,7,8 - 取代成分的特定混合物处理的人肝癌HepG2细胞中，分析了P4501A1依赖性7 - 乙氧基异吩恶唑酮 - O - 脱乙基酶（EROD）诱导的剂量 - 反应曲线，这与之前对大鼠肝细胞和H4IIE细胞的研究类似（施伦克等人，1991年）。与大鼠细胞相比，PCDDs在人HepG2细胞中的作用似乎较弱。例如，2,3,7,8 - 四氯二苯并 - 对 - 二噁英（2,3,7,8 - Cl4DD）的半数有效浓度（EC50）值分别比大鼠H4IIE细胞和肝细胞高8倍和19倍。将PCDDs的EC50值与2,3,7,8 - Cl4DD的EC50值进行比较，并表示为2,3,7,8 - Cl4DD当量（TEs）。尽管PCDDs的效力排名顺序相似，但发现某些PCDDs（1,2,3,7,8 - 五氯二苯并 - 对 - 二噁英；TE = 0.75和1,2,3,7,8 - 六氯二苯并 - 对 - 二噁英；TE = 0.61）的TEs高于大鼠系统。与大鼠细胞不同，在HepG2细胞中，直至其溶解度极限，用八氯二苯并 - 对 - 二噁英（Cl8DD）未检测到EROD的显著诱导。发现含有49种成分的PCDD混合物的实验测定TEs在很大程度上归因于其2,3,7,8 - 取代成分的加和效应。
