Expression of heme oxygenase in arsenic-resistant human lung adenocarcinoma cells.
We have established arsenic-resistant cells (CL3R) and their subclones from a human lung adenocarcinoma cell line (CL3). CL3R cells and their subclones were maintained in the presence of 4 microM sodium arsenite. They were 6-fold more resistant than CL3 cells to arsenite. Heme oxygenase was expressed in CL3R cells and their subclones, as demonstrated by electrophoretic analysis, Northern blotting, and enzyme activity assay. When CL3R15 cells were grown in arsenite-free medium, their arsenite resistance declined in parallel with their decreasing heme oxygenase activity. Tin-protoporphyrin, a heme oxygenase inhibitor, was found to increase the toxicity of arsenic to CL3R cells. Expression of heme oxygenase might therefore be involved in the mechanism of arsenic resistance. CL3R cells were also shown to be cross-resistant to oxygen-radical generating agents, such as menadione and Adriamycin. Furthermore, sodium arsenite treatment dose-dependently increased the dichlorofluorescein fluorescence in CL3 cells but not in CL3R15 cells. These results suggest that heme oxygenase plays an important role in reducing cellular oxidants that are enhanced by sodium arsenite treatment.
Lee
T C
TC
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
Ho
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IC
D000230:Adenocarcinoma / Q000201:enzymology*; D018053:Arsenites / Q000633:toxicity*; D001483:Base Sequence; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D015870:Gene Expression; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology*; D008665:Metalloporphyrins / Q000633:toxicity; D008715:Methionine / Q000378:metabolism; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D011524:Protoporphyrins / Q000633:toxicity; D012333:RNA, Messenger / Q000096:biosynthesis; D017670:Sodium Compounds / Q000633:toxicity*; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D018053:Arsenites; D008665:Metalloporphyrins; D009838:Oligodeoxyribonucleotides; D011524:Protoporphyrins; D012333:RNA, Messenger; D017670:Sodium Compounds; C017947:sodium arsenite; D008715:Methionine; C032628:tin protoporphyrin IX; D006419:Heme Oxygenase (Decyclizing)