On control of the hematopoietic cell proliferation.

Hematopoietic cells, detected as spleen colony forming units (CFU-S), vary in their proliferation rate, and this can be investigated in vivo by determining the fraction of CFU-S synthesizing DNA. A large number of measurements of CFU-S number and the fraction synthesizing DNA has been obtained under standardized conditions in normal mice and after a single dose of arabinosyl cytosine (ara-C). These data are analyzed with respect to the correlation between the number of CFU-S and their DNA-synthesizing fraction since, in the past, it has been maintained that the CFU-S proliferation rate responds sensitively to changes in CFU-S numbers. The present analysis does not support this traditional view--it instead demonstrates that natural variations in CFU-S numbers occurring in the same range as those following ara-C do not trigger CFU-S proliferation. On the other hand, administration of ara-C triggers most of the surviving CFU-S into the cell cycle, while decreasing CFU-S numbers by only about 40%. Data are also presented showing changes of CFU-S numbers and their DNA-synthesizing fraction in mice given a single dose of cyclophosphamide (CY). CY reduces CFU-S numbers, but the fraction synthesizing DNA can be either increased or decreased depending on time after treatment. Both these experimental situations argue against a close relationship between CFU-S numbers and their proliferation rate and suggest a different or a more complex regulation.