Alteration of prostaglandin biosynthesis in rat chloroleukemic tumor.
Data from our present studies demonstrate the capability of a 105,000 X g pellet from rat normal bone marrow, turpentine-induced hyperplastic bone marrow, and chloroma tumor to transform precursor arachidonic acid into prostaglandins. The activity of the prostaglandin synthetase systems in these tissues is inhibited by the known nonsteroid antiinflammatory drug indomethacin and by two unsaturated fatty acids previously demonstrated in other tissues. Although the overall biosynthesis of prostaglandin E2 (PGE2) was higher in the hyperplastic bone marrow than in the chloroma tumor, the PGF2alpha:PGE2 ratio was markedly higher (8-fold) in the chloroma tissue. This latter increase was probably due to the increased transformation of PGE2 into PGF2alpha by the NADPH-dependent PGE2 9-ketoreductase (an enzyme that catalyzes the transformation of PGE2 and PGF2alpha). These results indicate the greater capability of the malignant chloroma tissue to form PGF2alpha than of nonmalignant hyperplastic bone marrow. Although the role of PGF2alpha in the malignant myelogenous leukemic tumor is presently unclear, its increased formation in this tissue suggests that this substance may play a role in the hyperproliferative process.
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism; D006965:Hyperplasia / Q000378:metabolism; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D007942:Leukemia, Experimental / Q000378:metabolism* / Q000473:pathology; D007951:Leukemia, Myeloid / Q000378:metabolism / Q000473:pathology; D011458:Prostaglandins E / Q000096:biosynthesis*; D011460:Prostaglandins F / Q000096:biosynthesis*; D051381:Rats
D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D011458:Prostaglandins E; D011460:Prostaglandins F; D006911:Hydroxyprostaglandin Dehydrogenases; D007213:Indomethacin