The major project in the laboratory is to determine the pathogenetic mechanisms involved in the development of mineral oil induced plasmacytomas in BALB/c mice. BALB/c mice are highly susceptible to developing these tumors while most other strains are resistant. BALB/c.DBA/2 and BALB/cAn.BALB/cJ congenic strains are being developed as model systems. The source of 'mutagenic' (carcinogenic) substances in this system are thought to be oxygen and lipid radicals that are generated by the phagocytosis of the oil and the agents that induce chromosome breaks, the consistent chromosome 15 translocations and the c-myc gene deregulation that occurs in over 95% of plasmacytomas. In collaborative studies with Katherine Sanford we have found that BALB/cAn mice have a defective ability to repair x-ray and light induced double stranded DNA breaks. We are attempting to find the genetic basis for this phenotype. A study of the histogenesis of plasmacytoma development has been completed which has shown progressive plasma cell proliferative lesions develop in BALB/c but not plasmacytoma resistant strains: BALB/cJ, C57BL/6, DBA/2, CDF1. A new rapid induction of plasmacytomas method has been developed which involves infecting pristane conditioned mice with recombinant retroviruses containing oncogenes.
