EFFECTS OF GAMMA-LINOLENIC ACID AND ARACHIDONIC-ACID ON CELL-CYCLE PROGRESSION AND APOPTOSIS INDUCTION IN NORMAL AND TRANSFORMED-CELLS

The effects of arachidonic acid (AA) and gamma-linolenic acid (GLA) on cell cycle progression and apoptosis induction, using flow cytometry, were compared on normal human skin fibroblasts, strain HSF43 with wil d type (wt) p53, large T antigen transformed HSF43 cells (line E8T4) w ith non functional p53, and on two lymphoblast cell lines, TK6 with wt p53 and WTK1 with mutant p53. AA and GLA caused similar dose (50, 75 and 100 mu g/ml AA and GLA) and time dependent (24 and 48 h) induction of apoptosis in each cell line. The degrees of the response of the fo ur cell lines were, however, different. The normal HSF43 cells were mo st resistant against apoptosis induction and the WTK1 cells most susce ptible. The apoptosis induction appeared to be independent of function al p53. Cell cycle progression was also similarly affected by AA and G LA in the two cell types. In the fibroblast type cells (HSF43 and E8T4 ) S- and G(2)/M-phase arrests were evident after 48 h exposure to AA a nd GLA, and in the lymphoblast cell lines (TK6 and WTK1) the cells wer e arrested in the G(1)-phase.