Immunologic selection against simian virus-40 transformed cells: Concomitant loss of viral antigens and early viral gene sequences

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Abstract
A clonal line of highly oncogenic spontaneously transformed mouse cells (T AL/N clone 3) was transformed in tissue culture by SV40 and subsequently recloned. The clone of SV-40 transformed cells (subclone 1) expressed SV-40 specific T (nuclear) and transplantation antigens but was 100 times less tumorigenic than the parent T AL/N clone 3 cells. When large numbers of subclone 1 cells (104-105) were injected into syngeneic AL/N mice, tumors were produced. From the tumors, cell lines were established in culture, all of which were consistently negative for T antigen. Tumor lines tested did not contain SV40-specific transplantation antigen and again became highly tumorigenic. The original subclone 1 cells contained about 1 copy of SV-40 DNA/diploid amount of cell DNA, and RNA complementary to the early region of the SV-40 genome. The T antigen-negative cells from tumor line 124 contained approximately 0.5 copy of SV-40 DNA/diploid equivalent and did not synthesize any detectable virus-specific RNA. Reassociation kinetic analysis with [HindII, Hind III, BamHI, HhaI and TaqI] restriction enzyme fragments of viral DNA demonstrated that the cells from tumor line 124 (and also the clones of this line) lost DNA sequences predominantly from the early region of the SV-40 genome. Apparently, a set of stably integrated SV-40 DNA sequences can be present in a cell without the expression of viral antigens.