Adriamycin tolerance in human mesothelioma lines and cell surface NADH oxidase.
Adriamycin tolerant human mesothelioma cell lines derived from a single tumor prior to either chemotherapy or radiation therapy and a susceptible cell line were investigated. Not only was growth resistant to low doses of adriamycin but an unusual pattern of resistance was encountered in which cells seemed to better tolerate high adriamycin doses than intermediate doses. The differential growth susceptibility of the tolerant lines compared to A549 lung carcinoma and the bimodal dose response correlated with differences in the specific activity of a plasma membrane-associated NADH oxidase (NOX). Plasma membrane fractions of high purity were isolated by aqueous two-phase partition and assayed directly. The NADH oxidase activity of the plasma membranes for the susceptible cell line was maximally inhibited by 1 microM adriamycin whereas the NADH oxidase activity of the tolerant lines was less and was maximally inhibited by 0.1 microM adriamycin with 1 and 10 microM adriamycin being less inhibitory than 0.1 microM adriamycin. The findings suggest a relationship between the growth response to adriamycin of the adriamycin tolerant mesothelioma lines and the activity of the plasma membrane-associated NADH oxidase activity of the cell surface in these cell lines.
Hedges
Kathryn L
KL
Department of Biological Sciences, Purdue University Calumet, Hammond, IN 46323, USA.
Morré
Dorothy M
DM
Wu
Lian-Ying
LY
Morre
D James
DJ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000378:metabolism / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D004361:Drug Tolerance; D006801:Humans; D008654:Mesothelioma / Q000188:drug therapy* / Q000201:enzymology; D009097:Multienzyme Complexes / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D009097:Multienzyme Complexes; D004317:Doxorubicin; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases