DIFFERENT MODES OF CELL-DEATH INDUCED BY 5-FLUORO-2'-DEOXYURIDINE IN 2 CLONES OF THE MOUSE MAMMARY-TUMOR FM3A CELL-LINE

The mode of cell death induced by 1 mu M 5-fluoro-2'-deoxyuridine (FdU rd) changed in a wild-type F28-7 clone of mouse mammary tumor FM3A cel ls after a six-month culture. In the original stocked F28-7 clone, FdU rd-induced cell death was accompanied by necrosis-like cell swelling a nd DNA fragmentation to 100-200 kbp. In subclone F28-7-A isolated from F28-7 cells, which had been cultured for six months, apoptotic bodies and nucleosomal DNA-ladder fragments were observed with the treatment . Furthermore, we investigated the differences in FdUrd-induced intrac ellular signals between these clones. In F28-7 cells, FdUrd induced in creases in caspase-3-like activity, and the mRNA levels of the c-jun, c-fos and c-myc genes, which were greater and earlier than those in F2 8-7-A cells. Moreover, intracellular acidification occurred in F28-7-A cells treated with FdUrd, though it was not observed in F28-7 cells. These findings suggest that FdUrd-induced cell death occurred through the death program to cell lysis (necrosis) without apoptosis when the induction of these intracellular signals was very high and when intrac ellular acidification was deficient. Investigation of the differences in the mode of FdUrd-induced cell death between these clones would be important for elucidating the molecular mechanism of pivotal events gu iding cells toward either apoptosis or necrosis. (C) 1998 Academic Pre ss.