The effect of daunomycin on human cells in vivo and in vitro

Cytogenetic and morphologic abnormalities in bone marrow and peripheral blood and biochemical changes in peripheral blood leukocytes were studied after in‐vivo and in‐vitro treatment with daunomycin. Seven patients with acute lymphocytic or granulocytic leukemia were studied; the total dose varied from 80 to 420 mg/m². The highest percentage of major chromosomal aberrations (80 to 90%) appeared right after treatment in vivo. These aberrations disappeared within 1 or 2 weeks and consisted of chromatid breaks, fragments, chromatid exchanges, ring chromosomes, dicentrics or extensive fragments. Prominent morphologic abnormalities included megaloblastic transformation of both the myeloid and erythroid series and increased cytoplasmic vacuolization. Aneuploid cells lines from two patients showed less change after daunomycin treatment than did normal diploid cells. The daunomycin dose threshold in vitro was narrow: 3 μg/ml of culture caused death of the entire cell population, while 0.03 μg/ml of culture produced little chromosomal damage. The in‐vitro studies on normal human lymphocytes indicate that daunomycin affects RNA and DNA synthesis and that it interferes with the cell cycle during the G2 period. This drug appears to have the unique capacity to delay the onset of mitosis in cells which have already synthesized DNA.