Effects of 5-bromo-2'-deoxyuridine on arachidonic acid metabolism of neuroblastoma and leukemia cells in culture: a possible role of endogenous prostaglandins in tumor cell proliferation and differentiation.

Effects of 5-bromo-2'-deoxyuridine (BrdU) were studied on two neuroblastoma and two leukemia cell lines, in terms of the relationship between prostaglandin (PG) synthesis and cell growth/differentiation. After treatment with BrdU (5 micrograms/ml), cell growth of the 4 cell lines was inhibited and one neuroblastoma cell line (GOTO) showed flattened morphology with positive S-100 protein, one of the differentiation markers for Schwann or glial cells. In the 4 cell lines, BrdU treatment reduced [1-(14)C]-arachidonic acid incorporation into phosphatidylinositol and phosphatidylethanolamine and was associated with an increase into phosphatidylcholine and triglyceride. BrdU treatment also increased fractions of 6-keto-PGF1 alpha and PGF2 alpha, with a decreased TXB2 fraction. The decreased ratio of TXB2/6-keto-PGF1 alpha or increased 6-keto-PGF1 alpha fraction correlated significantly with cell growth inhibition, suggesting that the changes in the balance of endogenous PGs might be associated with BrdU-induced cell growth inhibition with or without differentiation of neuro-blastoma and leukemia cells in culture.