Cellular targets of adriamycin-induced damage in Escherichia coli.
The cellular targets of adriamycin (ADR) activity were studied in Escherichia coli by following colony forming ability and various cellular functions. The parameter exhibiting the best correlation with mortality was inhibition of RNA synthesis. Total DNA synthesis was inhibited to a lesser extent, but may reflect a concurrent inhibition of replication and stimulation of DNA repair activity. Protein synthesis, membrane function and rate of oxygen consumption were affected later. No extensive DNA fragmentation was observed. The inhibition of RNA synthesis was independent of the stringent response and of inhibition of DNA synthesis induced by nalidixic acid. ADR activated the SOS repair system, and the lesions induced by the drug could be repaired by recA dependent functions. These results indicate that the primary activity of ADR was directed against the DNA and interfered with the DNA template function.
D000255:Adenosine Triphosphate / Q000032:analysis; D001693:Biological Transport, Active / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects; D007930:Leucine / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis
D012313:RNA; D004317:Doxorubicin; D000255:Adenosine Triphosphate; D004247:DNA; D007930:Leucine