N-methyl-N-nitrosourea-induced T-lymphomas of AKR/J mice contain somatically acquired ecotropic-like murine leukemia proviruses.

We have studied somatically murine leukemia proviral integrations in primary N-methyl-N-nitrosourea (MNU)-induced thymic lymphomas of AKR/J mice. The majority of MNU-induced lymphomas contain newly acquired murine leukemia proviral sequences. In contrast to spontaneous AKR/J lymphomas which contain multiple integrations of mink cell focus-forming recombinant proviruses, MNU-induced lymphomas contain ecotropic-related proviruses. This conclusion was based on the demonstration that EcoRI- and PvuII-digested DNA from MNU-induced lymphomas contains new 3' proviral-cellular junction fragments that hybridize with the ecotropic-specific pAKV-4 and pAKV-5 hybridization probes. Also, EcoRI/PstI double digests of DNA from MNU-induced lymphomas revealed that the acquired proviruses do not contain an internal 3' EcoRI site characteristic of mink cell focus-forming recombinant viruses. The proviral integration patterns suggest that MNU-induced lymphomas are clonal or oligoclonal in nature. This conclusion is supported by comparison of proviral integration patterns in lymphomas obtained from thymus and spleen of individual mice, and by analyses of T-cell receptor beta-chain gene rearrangements. The frequent occurrence of ecotropic-related proviral sequences in MNU-induced lymphomas suggests that these newly acquired proviruses may play a role in tumor development.