The effect of induction of hemoglobin synthesis in cultured Friend cells on the number of initiation sites for replication and transcription.
It was found that differentiation of murine erythroleukemia cells can be induced by 5-fluorodeoxyuridine (FudR), amethopterin and alpha-aminoisobutyrate. Each of these compounds is believed to delay the onset of DNA synthesis. Since relief of the FudR block to DNA synthesis by addition of thymidine can increase the number of initiation sites for replication (Taylor, 1977), the effect of various inducers and inhibitors of differentiation of Friend cells upon the relative number of initiation sites for replication and transcription was investigated. Very efficient inducers of hemoglobin synthesis, hexamethylene bisacetamide (HMBA) and dimethylsulfoxide (DMSO), increase the number of initiation sites for transcription and HMBA also increases the number of functional initiation sites for replication. Two other compounds that induce differentiation of Friend cells, low levels of actinomycin D and FudR, did not increase the number of initiation sites for transcription. Compounds that prevent induction of hemoglobin synthesis by HMBA and DMSO include 5-bromodeoxyuridine (BrdU) and novobiocin. Both of these compounds were found to decrease the number of functional initiation sites for transcription and it is known that both compounds reduce the number of initiation sites for replication. The relation between initiation of replication and transcription, and its effect upon differentiation of erythroleukemia cells is discussed.
D000081:Acetamides / Q000494:pharmacology; D000621:Aminoisobutyric Acids / Q000633:toxicity; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005467:Floxuridine / Q000633:toxicity; D006454:Hemoglobins / Q000096:biosynthesis* / Q000235:genetics; D007700:Kinetics; D007942:Leukemia, Experimental / Q000503:physiopathology*; D008727:Methotrexate / Q000633:toxicity; D051379:Mice; D014158:Transcription, Genetic / Q000187:drug effects
D000081:Acetamides; D000621:Aminoisobutyric Acids; D006454:Hemoglobins; D005467:Floxuridine; C100049:2-aminoisobutyric acid; C014026:hexamethylene bisacetamide; D008727:Methotrexate; D004121:Dimethyl Sulfoxide