Plasmacytoma induction in specific pathogen-free (SPF) bcl-2 transgenic BALB/c mice

Germ-free (GF) and specific pathogen free (SPF) BALB/c mice are refractory to plasmacytoma induction by pristane (McIntire and Princler, 1969, Byrd et al 1991). It was therefore suggested that MPC development may depend on an tigenic stimulation. If so, it may conceivably act by preventing the apopto tic elimination of tumor precursor cells. We have tested this idea by eleva ting the apoptotic threshold by the introduction of a bcl-2 transgene. We h ave found that MPCs could be induced by pristane oil in transgene carrying SPF mice. An E mu activated bcl-2 transgene was introduced into SPF BALB/c mice. The mice were used after two backcrosses (BC-2). Pristane oil treatme nt was started at 4 to 6 weeks of age (3 x 0.3 ml via i. p. at monthly inte rvals). For each transgene carrier a transgene negative littermate was used as control. Fifteen of 24 (63 %) transgene carriers developed plasmacytoma s after latency periods between 67 and 146 days (X = 112 +/- 30 days) after the first pristane injection. Five additional transgene carriers developed lymphoma (3 cases) or mixed MPC and lymphoma (2 cases). In contrast, no tu mors developed in 16 transgene negative littermates that were kept >300 day s under observation. Karyotyping showed that 10/15 (66 %) of the MPCs carri ed a T(12;15) translocation, 4/15 (27 %) carried both T(12;15) and T(6;15) translocations in the same metaphase plate, and 1/15 (7 %) was translocatio n free. A T(12;15) translocation was also detected in one of the 2 mice wit h mixed tumor type. Pristane treated bcl-2 transgenic C57B1/6 mice remained tumor free, although T(12;15) translocation carrying cells were found in t he peritoneal fluid of 4/20 mice 176 days after pristane.