Abstract
Two neoplastic cell strains derived from the C57BL/6 mice, P4bis originating from normal adult lung tissue “spontaneously” transformed in vitro, and TBLC2 developed from a methylcholanthrene‐induced sarcoma, were both infected in vitro with Rauscher leukemia virus. Consecutive to this infection, the tumor‐producing capacity of these cells, which continued to multiply normally in vitro, dropped considerably when checked in syngeneic mice. This was evidenced by a dramatic decrease of takes and a significant prolongation of latency period. The high leukemogenic RRL^+^ and the low leukemogenic RCL^−^ virus variants were equally efficient in infecting cells in vitro and producing a decrease of their tumorigenic potential in vivo. This decrease coincided with the massive appearance in the cells and culture supernatant of C‐type particles and of a new surface antigen reacting specifically in the immunofluorescence test with anti‐Rauscher virus serum. The specific immunological nature of decreased tumorigenicity was confirmed by the fact that the rejection of the virus‐infected cells could be prevented by total irradiation of intact recipient animals, whereas animals preimmunized and later irradiated continued to reject the infected cells. On the other hand, the rare tumors which appeared in non‐irradiated adults after a long latency period were composed of virus‐free cells whereas cells from tumors obtained by inoculation of new‐born animals regularly contained the virus and were rejected when grafted on normal adults.
In another series of experiments, in P4bis cell cultures, subjected in vitro to the action of methylcholanthrene for several months, the appearance of C‐type particles and of a new cell‐surface antigen reacting specifically in the immunofluorescence test with anti‐Gross leukemia serum, was observed. The untreated control cultures remained negative for C particles and antigen. The appearance of this chronic C‐type virus infection coincided, here again, with a considerable decrease in tumor‐producing capacity of the P4bis cells as checked in syngeneic mice.
The reported results are discussed in the context of the possible role played by chronic infections, especially by widely spread non‐pathogenic variants of leukemia viruses, in the “heterogenization” of tumor cells contributing to their rejection triggered by an immune reaction of the host.