INDUCTION OF PLASMACYTOMAS WITH SILICONE GEL IN GENETICALLY SUSCEPTIBLE STRAINS OF MICE

Background: Plasmacytomas can be induced in high frequency in suscepti ble strains of mice by the intraperitoneal introduction of plastics or paraffin oils, including the chemically defined oil pristane (2,6,10, 14-tetramethglpentadecane). These materials persist in the peritoneal cavity, where they induce chronic inflammation during the long periods before plasmacytomas develop. Such plasmacytomas appear to arise from B cells carrying chromosomal translocations that affect c-myc transcr iption. Purpose: Because silicone gels are in widespread medical use a nd share many of the characteristics of other materials known to be in ducers of plasmacytomas, we wished to determine their capacity to indu ce plasmacytomas in mice. Methods: In a series of parallel experiments , corn oil, pristane, silicone oil (dimethylpolysiloxane), or silicone gel from commercially obtained mammary implants was injected intraper itoneally into plasmacytoma-susceptible BALB/cAnPt-A and congenic BALB /cAnPt.DB A/2-Idhl-Pep3 mice, as well as into plasmacytoma-resistant C 57BL/6N, C3H/HeJ, DBA/2N, and (BALB/c x DBA/2)F1 mice. Mice were exami ned at least once every 2 weeks for signs of abdominal tumor or weight loss and screened every 4-6 weeks for; peritoneal-plasmacytoma cells by peritoneal lavage. Tissues were examined by histologic and immunohi stechemical techniques. Metaphase chromosome spreads were made from as citic plasmacytomas without Colcemid treatment, and metaphase plates w ere G-banded according to standard techniques. The t(12;15) or t(6;15) translocation chromosomes were identified under the microscope in at least five metaphase plates of high banding quality. Mice were autopsi ed 125-400 days after the injection of test material. Gas chromatograp hy and mass spectrometry were utilized to determine the composition of the silicone oil and silicone gel used in the injections. Results: Th e silicone gels tested induced plasmacytomas in BALB/cAnPt-A and BALB/ cAnPt.DBA/2-Idhl-Pep3 mice. Neither corn oil used as a control nor 100 0-centistoke or 12500-centistoke dimethylpolysiloxane induced plasmacy tomas in these mice. The plasmacytomas were transplantable in syngenei c hosts. Cytogenetic studies of 41 silicone-induced plasmacytomas show ed that 30 had t(12;15) translocations, eight had t(6;15) translocatio ns, and three had no translocations. Conclusions: The silicone gels us ed in mammary implants, which contain a complex mixture of different s iloxanes, induced peritoneal plasmacytomas in genetically susceptible mice. Silicone gels provide new chemically defined materials that are effective inducers of plasmacytomas in BALB/cAnPt-A and BALB/cAnPt.DBA /2-Idh1-Pep3 mice. Further studies will be required to determine which of the components of these gels are the active materials.