Synergistic action of radiation and virus in induction of leukemia in rats.

More than 50% of Wistar/Furth (W/Fu) strain rats, which received combined treatment with a fractionated total-body X-irradiation and an injection of a mouse leukemia virus (Gross virus), developed leukemia within 7 months following treatment. The majority of the induced leukemias were thymic lymphomas with a short latency period similar to those observed in susceptible strains of mice and W/Fu rats after the neonatal inoculation of this virus. Also, a few cases of nonthymic lymphoid leukemia and myeloid leukemia of the chloroma type occurred with a longer latency period. Persistence and multiplication of the inoculated virus in leukemic rats were suggested by the development of leukemia in recipients which were inoculated at birth with cell-free filtrates prepared from these leukemic rats. In contrast to these findings, no leukemia occurred among rats which received either fractionated total-body X-irradiation alone or virus inoculation alone. As to the mechanism of leukemogenic synergism of radiation and virus, it is suggested that radiation acts as a modifier for both the physiologic state of the target cell of the virus and the immunologic responsiveness of the host. Thus, it might promote an interaction between the target cell and virus and a proliferation of antigenically altered leukemic cells.