Radiogenic myeloid leukemia of the RF mouse was passaged in unirradiated newborn and adult recipients of the same strain by intravenous inoculation of leukemic spleen cell suspensions, cell-free filtrates of such suspensions, and centrifuged (presumably cell-free) spleen extracts and blood plasma. The incidence of leukemia in inoculated mice increased on successive passages, and the induction period decreased. After the fifteenth passage, supernatant fluid from centrifuged (30,000 × g for 60 minutes) leukemic spleen cell suspension and blood plasma transmitted the disease within 70 days to 30–60 per cent of unirradiated adult recipients. Although the leukemia retained its granulocytic and myelocytic character on serial transmission in adults, a significant number of newborn recipients developed thymic lymphomas within 90 days after inoculation, suggesting either that the same agent can induce both types of leukemia, depending on the influence of host factors, or that more than one leukemogenic agent was present in our filtrates.
Leukemogenic activity was not detected in filtrates of brain or spleen tissue from donors with primary radiogenic myeloid leukemia on inoculation into unirradiated recipients or those given 150–300 r of whole-body x-rays; however, such filtrates increased the incidence of myeloid leukemia on inoculation into mice previously exposed to 450 r whole-body x-radiation, suggesting that radiation may enhance susceptibility to an agent present in otherwise undetectable amounts or form. The relatively short latency of the filtrate-induced leukemia (less than 6 weeks) contrasted sharply with the characteristically long latency of the radiation-induced leukemia (6–50 weeks), from which it may be inferred that the leukemogenic action of radiation is not merely the prompt “activation” or liberation of latent leukemia virus.