In order to elucidate the relationship between the development of Friend leukemia and erythroid differentiation in affected organs, C3H/He mice were given injections of high doses (about 2 × 104 spleen focus-forming units) of Friend leukemia virus, and changes in the heme synthesis rate, in responsiveness to erythropoietin in vitro, and in RNA-dependent DNA polymerase activity were investigated.

By the 6th day following Friend leukemia virus inoculation, hyperbasophilic “Friend cells” resembling proerythroblasts became dominant in the spleen. The heme synthesis rate in the infected spleen cells started to increase 14 days after inoculation and reached a plateau at a level about five times higher than that of the uninfected control spleen cells after about 22 days. With respect to the response of the spleen cells to erythropoietin in vitro, however, while a normal response had been observed 4 hr after the inoculation, no response could be detected at 24 hr and thereafter. RNA-dependent DNA polymerase activity in the spleen cells began to increase on the 4th day, attaining a peak on the 8th and 10th days and decreasing markedly thereafter. Enzyme activity again increased on the 28th day. These results suggest that Friend leukemia virus affected the erythropoietin-responsive cells at a very early stage of infection, before morphological changes in the spleen cells or increases in RNA-dependent DNA polymerase activity had been observed.


This investigation was supported in part by a Research Grant for Specific Disease from the Ministry of Health and Welfare.

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