The induction of plasmacytomas (PCTs) in the peritoneal cavity of BALB/cAn mice by plastics, paraffin oils or silicone gels is a model system for identifying the steps and stages of neoplastic development. An early oncogenic event in plasmacytomagenesis (PCTgenesis) is a chromosomal translocation that illegitimately recombines c-myc with an Ig locus gene resulting in deregulation of c-myc transcription. Recentevidence from a highly sensitive nested PCR detection method indicates this step probably takes place before the introduction of the peritoneal inducing agent. A second consistent tumor suppressor phenotype, i.e., loss of functional TGF-beta receptors has been identified. Many of the steps in PCTgenesis take place in the chronic inflammatory microenvironment of the oil granuloma induced by pristane or silicone gels. PCTgenesis can be dramatically inhibited by the chronic administration of the cyclooxygenase inhibitor, indomethacin. This suggests that a prostaglandin produced by an accessory cell is an important effector in plasmacytoma develoment. Current studies are aimed at elucidating the mechanism of indomethacin inhibition and implicating a prostaglandin, e.g., PGE2 in this process. Recent work demonstrating the resistance of BALB/c.CBA/N congenic mice to PCT induction implicates the btk pathway and the ability of B cells in BALB/c mice to respond to auto and environmental (gut flora) antigens in PCTgenesis. We are studying the role of other environmental factors relating to microbial flora, diet, i.e., fatty acid content and cage bedding on PCTGEN. - c-myc, chromosomal translocations, cyclooxygenase, IL-6, indometharin, plasmacytoma, prostaglandins, susceptibility/resistance genes, TGF beta, xid, B-1 cells,
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