EFFECT OF MODIFIERS OF ARACHIDONIC-ACID METABOLISM ON RADIATION TRANSFORMATION AND EICOSANOID FORMATION IN C3H 10T1/2 CELLS/

In these studies, we performed experiments designed to elucidate the r ole that arachidonic acid metabolism plays in oncogenic transformation in vitro. The levels of TxB(2) and 6-keto-PGF(1 alpha) were elevated in cells treated with X-rays. A significant increase in the levels of these eicosanoids was observed following irradiation. Treatment of cel ls with the anticarcinogenic protease inhibitors, Bowman-Birk Inhibito r (BBI) and N-tosyl-L-phenylalanine chloromethyl ketone (TPCK), signif icantly reduced the levels of TxB(2) and 6-keto-PGF(1 alpha) present. Indomethacin treatment significantly reduced the levels of TxB(2) and 6-keto-PGF(1 alpha) to < 10% of those present in untreated or irradiat ed cells. We also report that addition of lipoxygenase or minoxidil [a selective inhibitor of prostacyclin (PGI(2) synthetase] led to a high ly significant decrease in transformation. In addition, minoxidil trea tment resulted in a significant reduction in the levels of 6-keto-PGF( 1 alpha) in irradiated cells. Our results suggest the hypothesis that the relative levels of 6-keto-PGF(1 alpha) are important in radiation induced transformation.