INDOMETHACIN IS A POTENT INHIBITOR OF PRISTANE AND PLASTIC DISC INDUCED PLASMACYTOMAGENESIS IN A HYPERSUSCEPTIBLE BALB C CONGENIC STRAIN/

Continuous indomethacin (INDO) administration in the drinking water (1 0 to 20 mu g/mL) profoundly inhibited plasmacytoma (PCT) development i nitiated by three 0.2- or 0.5-mL intraperitoneal (i.p.) injections of pristane in hypersusceptible BALB/c.DBA/2-ldh1-Pep3 congenic mice. The most effective inhibitions were obtained with continuous INDO treatme nt. When treatment was delayed until 50 to 60 days after the first pri stane injection, there was approximately a 50% reduction in PCT incide nce. The primary action of pristane is the induction of a chronic infl ammation in the peritoneal connective tissues and the formation of a m icroenvironment where PCTs develop, INDO, a powerful inhibitor of pros taglandin synthases (cyclooxygenases 1 and 2), did not inhibit the for mation of mesenteric oil granuloma nor the appearance of cells in this chronic inflammatory tissue carrying c-myc illegitimately joined to a n Ig heavy chain switch region, ie, the t(12;15) chromosomal transloca tion. INDO inhibited PCT induction by the i.p. implantation of 21 x 2 mm polycarbonate discs. These solid objects predominantly induce the f ormation of a patchy fibroplastic tissue on contacting peritoneal surf aces. These and previous data indicate that indomethacin inhibits an i ntermediate stage in PCT development after the arrival of cells bearin g the T(12;15) translocation in the oil granuloma and before these cel ls acquire transplantability to a pristane-conditioned host. The biolo gical mechanism that explains how INDO inhibits PCT development is not yet established but appears to result from decreased production of pr ostaglandins in chronic inflammatory tissues (oil granuloma, fibroplas ia), suggesting that prostaglandins play an active role in oil and sol id plastic induced PCT formation. This is a US government work. There are no restrictions on its use.