Ferrokinetic studies were performed i n 14 male patients with cancer who were given one of 5 different chemotherapeutic agents (methotrexate, fluorouracil, actinomycin D, hydroxyurea, galactoflavin). These drugs, which are capable of suppressing erythropoiesis via different mechanisms, produced similar alterations in ferrokinetics. T h e characteristic effects were a prolonged plasma disappearance of radioiron, a decreased uptake of radioiron by erythrocytes, a high uptake by the liver and a low uptake by the sacral marrow. Radioiron incorporated by the liver was released very slowly, which indicated that storage iron had been labeled. T h e changes observed with these drugs were similar to effects produced in previous studies with nitrogen mustard.
F l E R ?'HE AUhfINISTKATlON OF NITROGEN
A mustard (HN,) to human subjects the half-time for plasma radioiron clearance and the plasma iron concentration have been reported to increase for several days and then decrease.' Studies from this laboratory10 have confirmed these findings and also have shown that intravenously injected HN, inhibited temporarily the incorporation of radioiron into erythrocytes and depressed the erythrocyte uptake of radioiron. When radioiron was injected 2 to 4 days after H N 2 administration, the isotope was taken u p predominantly by the liver and to a smaller extent by the spleen. T h e slow release of radioiron from the liver and spleen suggested that it was contained in ;I stable "storage" pool. T h e half-time for disappearance of iron in this pool was estimated at 6 months or longer. Other studies from this laboratory11 have shown that in the dog treated with HN, the injected radioiron labels parenchymal hepatic cells and after 2 weeks is uniformly distributed in the liver, largely as ferritin in cytoplasmic sap.
T h e present studies were designed to determine whether the aberrations of ferrokinetics produced with HN, were unique for this drug.