Effect of melphalan on delta-aminolevulinic acid synthetase in the spleen, bone marrow and liver of rats.

The effect of melphalan, an antineoplastic alkylating agent, on the activity of delta-aminolevulinic acid synthetase (ALA-S) was studied. When given in a single oral dose (20 mg/kg) to male rats. ALA-S activity in the spleen rapidly declined, reaching 9% of controls 7 days after administration. A return to control values occurred after 10 days, followed by a rebound increase in activity to 180% of controls at day 15. After melphalan administration, a gradual loss in spleen weight was observed until day 10, followed by a rebound increase in spleen weight at day 15. Spleen heme oxygenase activity was induced to 243% of controls 7 days after melphalan administration. However, by 20 days the activity was only 55% above controls. Bone marrow ALA-S activity declined to 38% of controls 3 days after treatment, followed by a return to controls after 7 days. The return to control values at day 15 was accompanied by a shift in the differential white blood cell count to the segmented form. Red blood cell counts and hemoglobin content were decreased to 77% of controls at day 7. Liver ALA-S was not appreciably affected by melphalan except for a decrease to 56% of controls at day 7. It is concluded that melphalan depresses the level of activity of the erythroid form of ALA-S in spleen and bone marrow but has less effect upon the level of activity of the nonerythroid form in the liver.