Proviral structure and differentiation antigen phenotype of spontaneous and chemically induced AKR lymphomas

AKR mice develop spontaneous thymomas after 6 months of age due to a novel class of murine leukemia viruses that are generated by a series of genetic recombinations between endogenous proviral loci. AKR mice also are more susceptible to N-methyl-N-nitrosourea (MNU)-induced thymomas than are low-leukemia-incidence mouse strains. To determine whether virally and chemically induced lymphomagenesis proceeds by similar pathways in AKR mice, spontaneous and MNU-induced thymic lymphomas were analyzed for a DNA restriction linkage generated during spontaneous tumor development by recombination between envelope genes of endogenous murine leukemia proviral loci. DNA from spontaneous thymic lymphomas invariably contained a restriction fragment characteristic of recombinant murine leukemia virus etiology, while four of five MNU-induced thymic lymphomas did not show this restriction linkage. In addition, analysis of lymphocyte differentiation antigen profiles indicated that MNU-induced lymphomas represent a more immature stage of T-cell differentiation than the majority of spontaneous lymphomas. These data suggest that there are fundamental differences in the mechanisms of induction of virally and chemically induced thymic lymphomas in AKR mice.