Effect of Rauscher leukemia development on DNA synthesis by hematopoietic CFU-S

The effect of Rauscher viral leukemia on the number of colony forming cells (CFU-S) in the spleen has been measured as a function of time after virus administration. These were increased substantially after the first week, reaching a maximum at 2 weeks, after which they decreased in number. Determination of the proportion of these CFU-S which were in DNA synthesis was carried out using the in vitro 3HTdR suicide technique. Within 4 hours of injection of the virus the number of spleen CFU-S which could be inactivated by in vitro 3HTdR exposure increased to 20.9% from a normal mean value of 10.2%. For the next 2 weeks the proportion of CFU-S responding to tritiated thymidine exposure remained at the same value of approximately 20%; the change in number of surviving CFU-S roughly paralleled the change in total colony forming cells. In the third week after virus injection, the proportion of CFU-S which was inactivated by 3HTdR decreased to the point where it could no longer be detected, even though the total number of CFU-S was elevated several fold over the normal. These findings indicate that infection with moderate dose levels of Rauscher virus does result in a measurable early increase in the proportion of cells in DNA synthesis. However, the failure to detect further substantial increases as the disease develops suggests that the virus of itself is not an initiator of all the steps of DNA synthesis. Rather, it would appear that it is to some degree dependent upon other aspects of normal DNA synthesis which remain under control of the cell.