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 role that arachidonic acid metabolism plays in oncogenic transformation in vitro. The levels of TxB2 and 6-keto-PGF1 alpha were elevated in cells treated with X-rays. A significant increase in the levels of these eicosanoids was observed following irradiation. Treatment of cells with the anticarcinogenic protease inhibitors, Bowman-Birk Inhibitor (BBI) and N-tosyl-L-phenylalanine chloromethyl ketone (TPCK), significantly reduced the levels of TxB2 and 6-keto-PGF1 alpha present. Indomethacin treatment significantly reduced the levels of TxB2 and 6-keto-PGF1 alpha to < 10% of those present in untreated or irradiated cells. We also report that addition of lipoxygenase or minoxidil [a selective inhibitor of prostacyclin (PGl2) synthetase] led to a highly significant decrease in transformation. In addition, minoxidil treatment resulted in a significant reduction in the levels of 6-keto-PGF1 alpha in irradiated cells. Our results suggest the hypothesis that the relative levels of 6-keto-PGF1 alpha are important in radiation induced transformation.
Billings
P C
PC
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Maki
P A
PA
Kennedy
A R
AR
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism*; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000528:radiation effects; D007213:Indomethacin / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D008914:Minoxidil / Q000494:pharmacology; D008954:Models, Biological; D011480:Protease Inhibitors / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000378:metabolism*; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology; D014358:Trypsin Inhibitor, Bowman-Birk Soybean / Q000494:pharmacology; D014965:X-Rays
D001095:Arachidonic Acids; D011480:Protease Inhibitors; D014358:Trypsin Inhibitor, Bowman-Birk Soybean; D014108:Tosylphenylalanyl Chloromethyl Ketone; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D008914:Minoxidil; D007213:Indomethacin