THE EFFECT OF INHIBITORS OF ARACHIDONIC-ACID METABOLISM ON PROLIFERATION AND DEATH OF TUMOR-CELLS

The effect of inhibitors of arachidonic acid metabolism on proliferati on and death of tumor P-388 cells in a broad concentration range was s tudied. Cell proliferation,ras estimated by the metaphase frequency an d the proportion of cells in S phase; cell death was determined from l ysis, staining of cells with trypan blue, nuclear damage, percentage o f cells with subdiploid DNA and the type of DNA fragmentation. It was shown that low concentrations of phospholipase A(2) and lipoxygenase i nhibitors stimulated the proliferation of P-388 cells. At higher conce ntrations, the inhibitors suppressed cell proliferation by blocking th e G(1)-S transition and induced cell death of the apoptosis type. Indo methacin, an inhibitor of cyclooxygenase, did not initiate cell death, nor did it affect the proliferation of P-388 cells at concentrations of up to 10 mu M. (C) 1995 Federation of European Biochemical Societie s.