INCREASED DT-DIAPHORASE ACTIVITY IN TRANSFORMED AND TUMORIGENIC PANCREATIC ACINAR-CELLS

Pancreatic acinar cells from rats treated in vitro with 5-azacytidine and/or transfected with an activated c-H-ras demonstrated transformati on and tumorigenic phenotypes. DT-diaphorase (NAD(P)H:quinone oxidored uctase) activity was determined in these non-tumorigenic (3AP) and tum origenic cells (T3AP and T5AM). T5AM cells were those treated with 5-a zacytidine and further treated with N'-methyl-N'-nitro-nitrosoguanidin e. Higher levels of enzyme activity were found in transformed cells wh en compared to that in control cells (>15-fold, 3AP cells; >40-fold, T 3AP cells; >20-fold T5AM cells). In contrast, NADPH-cytochrome c reduc tase activity was decreased in transformed cells (>10-fold, 3AP cells; >20-fold, T3AP cells; >10-fold, T5AM cells). These studies demonstrat ed that pancreatic acinar cells are capable of undergoing alterations in enzyme activity patterns when transformed and that DT-diaphorase ma y be a good marker for malignant transformation.