UPTAKE, EFFLUX, AND HYDROLYSIS OF ACLACINOMYCIN-A IN FRIEND-LEUKEMIA CELLS

  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (5) , 1950-1954
Abstract
The kinetics of uptake by cells and nuclear incorporation of aclacinomycin A [ACM] was studied in Friend [mouse] leukemia cells. Uptake is very rapid. The intracellular concentration is maximum in 10 min and mainly (.apprx. 75%) localized in the nucleus. Most of the incorporated drug will disappear from the cell by a 2-step mechanism: efflux from the nucleus to the cytoplasm; and deglycosidation at C-7 to the alkavinone form in the cytoplasmic fraction. The cellular uptake was temperature dependent but was not prevented by sodium azide treatment. It may be related to the composition and to the dynamic structure of the cell surface membrane. Nuclear outward transport and deglycosidation were inhibited by sodium azide and low temperatures, suggesting that they are requlated by an active transport process and by an enzymatic activity, respectively. [ACM is a new antitumor antibiotic isolated from Streptomyces galileus MA 144-MI.].