Actinomycin D(AM), an inhibitor of DNA-dependent RNA synthesis, produces a reversible cessation of red blood cell production. This study examines the in vivo cellular uptake of 3H-AM in the hematological tissues and livers of B6D2FI mice. 3H-AM (sp. act. = 2.97 to 4.20 C/mmole) was given IV at a dose of 4.0 to 5.7 pg (14 pc) per mouse. Spleen, bone marrow, blood, and liver samples were taken for autoradiography at post-injection times of five minutes to 67 hours.
We have confirmed the rapid in vivo cellular uptake of AM; substantial quantities of the drug were in the nuclei within five minutes of IV administration.
Not all cell types became labeled. Erythroid, hepatic, lymphoid, and reticulo-endothelial (RE) cells and monocytes took up the label, whereas labeling of granulocytic elements was doubtful.
Most heavily labeled were liver cells (highest mean grain count = 110.1) and splenic RE(19.1) and erythroid (16.1) cells. Erythroid cells in the spleen were more heavily and more rapidly labeled than those in the bone marrow.
All nucleated erythroid maturational stages, in both the spleen and the bone marrow, were labeled, even at five minutes.
The time course of erythroid and hepatic labeling was quite different. Whereas early erythroid cells required six hours to become 100% labeled, liver cells were 100% labeled at five minutes and loss of hepatic labeling began as early as 15 to 30 minutes.