ANTI-FAS ANTIBODY INDUCES DIFFERENT TYPES OF CELL-DEATH IN THE HUMAN HISTIOCYTIC CELL-LINE, U937, AND THE HUMAN B-CELL LINE, B104 - THE ROLE OF SINGLE-STRAND DNA BREAKS AND POLY(ADP-RIBOSYL)ATION IN CELL-DEATH

We investigated the anti-Fas antibody-induced cell death in two different types of human cell lines, U937 and B104. IFN-γ increased the surface expression of Fas antigen and susceptibility to anti-Fas Ab-induced cell death of B104 and U937 cells. Anti-Fas Ab-induced death of U937 and B104 cells required neither a Ca2+ influx nor macromolecular synthesis. U937 cells treated with anti-Fas Ab represented apoptosis with DNA fragmentation, whereas anti-Fas Ab-treated B104 cells did not. Single-strand DNA breaks, however, appeared in the B104 cells. Zinc ions prevented DNA fragmentation and the morphological features of apoptosis in anti-Fas Ab-treated U937 cells, but did not inhibit cell death. However, zinc ions, when used in combination with the poly(ADP-ribosyl)ation inhibitors, inhibited anti-Fas Ab-induced U937 cell death. The inhibitors by themselves did not inhibit anti-Fas Ab-induced U937 cell death, but did inhibit anti-Fas Ab-induced B104 cell death. A substantial decrease in NAD pools was observed in anti-Fas Ab- treated B104 and U937 cells in parallel with the increase of DNA strand breaks before cell death became apparent. These results suggest the involvement of single-strand DNA breaks and poly(ADP-ribosyl)ation in the mechanisms of anti-Fas Ab-induced U937 and B104 cell death. © 1993 Academic Press. All rights reserved.