The major project in the laboratory is to determine pathogenetic mechanisms involved in the development of paraffin oil (pristane) induced plasmacytomas in BALB/c mice. BALB/cAn mice are highly susceptible to developing these tumors while most other strains are resistant. Over 95% of plasmacytomas induced by pristane have chromosomal translocations [rcpt(12;15), rcpt(6;15)] involving directly or indirectly the c-myc locus on chr 15. The principle problems on which we are working are: 1) to identify the genes that determine susceptibility to plasmacytoma induction; 2) to identify additional critical oncogenic mutations that cooperate with c-Myc using rapid plasmacytoma induction by infecting pristane-treated mice with transforming retroviruses that contain c-myc and a second cooperating oncogene; and 3) to determine the biological effects of pristane and how it acts in plasmacytoma induction. We have localized genes that determine resistance to plasmacytoma induction finding an exact location of one of the Pctr-l on chr 4. We have previously shown v-abl, v-Ha-ras, and v-raf-1 can cooperate with myc in transforming plasmacytomas and we are now testing new viruses prepared by K. Marcu that contain P53 Ha-ras Ela + H-ras and IL-6 + Ha-ras. Plasmacytomas have been induced with all three. We have developed BALB/c.DBA/2-congenic strains (fv-l(n/n) N19; Tol Fam3 N12, M.IA Nll) that carry various segments of chromosome 4 from the resistent DBA/2 strain. These congenic strains develop fewer plasmacytic proliferative lesions in the first 150 days and a much reduced incidence of plasmacytomas. Enumeration of the foci at between days 120-150 can predict plasmacytoma susceptibility. We are searching for the phenotypic effects of these genes and have evidence that genes involved in DNA repair on chr 4 may be a relevant phenotype.
