ADAPTATION TO OXIDATIVE STRESS - EFFECTS OF VINCLOZOLIN AND IPRODIONEON THE HEPG2 CELL-LINE

It is well known that the dicarboximide fungicides, vinclozolin and ip rodione, induce lipid peroxidation by means of oxygen activation in fu ngi, but their action on mammalian cells is not yet clear. We therefor e investigated the effect of 1- and 24-h treatments with vinclozolin a t concentrations of 25, 50, 100 mu g/ml and iprodione at concentration of 62.5. 125, 250 mu g/ml on malonaldehyde and free radical productio n and on reduced glutathione levels in the human HepG2 hepatoma cell l ine. The concentrations were chosen or the basis of neutral red cytoto xicity assays. One-hour treatment with the different concentrations of either vinclozolin or iprodione increased both malonaldehyde and free radical content and decreased reduced glutathione levels, whereas 24- h treatment decreased malonaldehyde content and free radical productio n, and increased reduced glulathione concentration. These results sugg est that the mammalian cells respond to the initial oxidative damage c aused by the two dicarboximide fungicides by means of a characteristic adaptative phenomenon within 24 h. This hypothesis is supported by th e antagonized effects caused by treatment with the two dicarboximide f ungicides and buthionine sulfoximine 0.5 mM, a specific and irreversib le inhibitor of reduced glutathione synthesis. The data confirm that t he two dicarboximide fungicides maintain their specific action in mamm alian cells, although this action is masked by adaptation. (C) 1998 El sevier Science B.V. All rights reserved.