Kikuchi H, Kato H, Mizuno M, Hossain A, Ikawa S, Miyazaki J, Watanabe M
Institute of Development, Aging, and Cancer, Division of Gene Research, Tohoku University, Sendai, Japan.
Arch Biochem Biophys. 1996 Oct 15;334(2):235-40. doi: 10.1006/abbi.1996.0451.
Three benzimidazole compounds, omeprazole (OP), thiabendazole (TBZ), and lansoprazole (LP), were compared with respect to the induction of CYP1A1-mRNA in human hepatoma cells, HepG2. OP was the most potent inducer among the three compounds, but LP was found to be a weak inducer. Induction by TBZ was at an intermediate level. None of these compounds induced CYP1A1-mRNA in a mouse hepatoma cell line, Hepa-1. The transient expression of mouse Cyp1a1-CAT gene into HepG2 cells showed that OP treatment of the transfectants induced CAT activity to the same degree as 2,3,7,8-tetrachlorodibenzo-p-dioxin treatment. Therefore, the cellular factors in human cells were able to work on the mouse regulatory element. The expression of human aryl hydrocarbon (Ah) receptor in the mouse Hepa-1 mutant cell line cl-19, which is defective in Ah receptor, did not increase the induction level of CYP1A1-mRNA by OP treatment. When the cultured medium of HepG2 cells in the presence of OP was added to the mouse Hepa-1 cell culture medium, CYP1A1-mRNA was not induced in Hepa-1 cells. It is thus concluded that metabolites of OP in human cells are not the ligands for the human Ah receptor. Therefore, in human cells, but not mouse cells, there must be an OP-sensitive activation factor for the human Ah receptor.
比较了三种苯并咪唑化合物，即奥美拉唑（OP）、噻苯达唑（TBZ）和兰索拉唑（LP）对人肝癌细胞HepG2中CYP1A1 - mRNA的诱导作用。OP是这三种化合物中最有效的诱导剂，但LP被发现是一种弱诱导剂。TBZ的诱导作用处于中等水平。这些化合物在小鼠肝癌细胞系Hepa - 1中均未诱导CYP1A1 - mRNA。将小鼠Cyp1a1 - CAT基因瞬时转染到HepG2细胞中，结果显示用OP处理转染细胞诱导CAT活性的程度与用2,3,7,8 - 四氯二苯并 - p - 二恶英处理相同。因此，人细胞中的细胞因子能够作用于小鼠的调控元件。在Ah受体缺陷的小鼠Hepa - 1突变细胞系cl - 19中，人芳烃（Ah）受体的表达并没有因OP处理而增加CYP1A1 - mRNA的诱导水平。当将存在OP时HepG2细胞的培养基添加到小鼠Hepa - 1细胞培养基中时，Hepa - 1细胞中未诱导出CYP1A1 - mRNA。由此得出结论，人细胞中OP的代谢产物不是人Ah受体的配体。因此，在人细胞而非小鼠细胞中，必定存在一种对人Ah受体敏感的激活因子。
