Inhibition of DNA synthesis in mammalian cells by daunomycin. Preferential inhibition of replicon initiation at low concentrations.
The effect of the intercalating agent daunomycin on DNA synthesis was studied in cultured bovine liver cells. At low daunomycin concentrations (1 and 2 muM) the rate of [3H]thymidine incorporation decreased progressively with the duration of exposure to the inhibitor. This was accompanied by a shift of nascent DNA intermediates of replicon size to higher sedimentation values on sucrose gradients, indicating that daunomycin preferentially affects the initiation of replicating units, both in asynchronous and synchronized cells. At high daunomycin concentrations (12 muM) the rate of chain growth was also markedly reduced. This was indicated by a rapid and nearly complete cessation of the [3H]thymidine incorporation and an accumulation of nascent DNA intermediates of low molecular weight. These observations are discussed in relation to a pre-fork mode of DNA synthesis.
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis* / Q000302:isolation & purification; D003630:Daunorubicin / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008970:Molecular Weight; D012093:Replicon / Q000187:drug effects*; D013936:Thymidine / Q000378:metabolism
D004247:DNA; D013936:Thymidine; D003630:Daunorubicin