Stimulation by amphotericin B of uridine transport, RNA synthesis and DNA synthesis in density-inhibited fibroblasts

Abstract

Amphotericin B is known to enhance the permeability of biological membranes through binding to membrane cholesterol. When added to density-inhibited 10T1/2 cells, this antibiotic stimulated uridine transport into the cells and its incorporation into RNA. This effect was not due to non-specific stimulation of the uptake of nutrients into the cells, since the antibiotic treatment of the cells brought about no change in either adenosine transport, nor its incorporation into RNA. A similar increase in uridine uptake caused by serum addition was observed within 1 h, whereas the increase stimulated by amphotericin B was preceded by a long lag of 10 h. Furthermore, amphotericin B increased uptake of thymidine into DNA and also caused a 20% increase in number of nuclei labeled with thymidine. The increase of thymidine uptake was inhibited by hydroxyurea. The results suggest that amphotericin B altered membrane permeability and allowed the initiation of DNA replication in density-inhibited fibroblasts.