Spermidine uptake by erythrocytes from normal and Lewis lung carcinoma (3LL) grafted mice: II. In vivo study.

During Lewis lung carcinoma (3LL) growth, red blood cell (RBC) spermidine (Spd) level evolution was proportional to the increase in tumor volume and inversely correlated with the decrease in tumor Spd concentration. Similarly, in cancer mice i.p. injected with [14C] Spd, the increasing amount of erythrocyte [14C] Spd was in proportion with tumor volume enhancement and linked to decrease in tumor tissue [14C] Spd concentration. After i.p. injection of [14C] Spd putrescine or [14C] spermine, contrary to normal mice, cancer mice provided [14C] Spd in their erythrocytes. When injected with [14C] methionine, [14C] polyamines were never found in normal or cancer mice erythrocytes. As previously noted in vitro, increasing amounts of polyamines produced by tumor tissue and excreted into blood would modify erythrocyte stroma proteins involved in the RBC [14C] Spd uptake process. These data obtained in vivo demonstrate the tumor origin of polyamines carried by erythrocytes. Since RBC polyamine levels are directly correlated with tumor progression, these experimental results reinforce the clinical use of this index of cell proliferation in malignant diseases with a short doubling time.