PD184352 releases the regular hypoxic reversible DNA replication arrest in T24 cells.
The oxygen dependent regulation of DNA replication is an essential property of proliferating mammalian cells. In human T24 bladder cancer cells, several hours of hypoxia leads to reversible DNA replication arrest and re-entry of oxygen induces a burst of replication initiation. This short communication provides strong evidence that PD184352 initiates DNA replication in living hypoxic cells without elevating the oxygen level. PD184352 releases the regular hypoxic replicon arrest, however, at a low intensity compared to the effect of reoxygenation. Moreover, PD184352 shows no effect on normoxically incubated as well as reoxygenated T24 cells.
Martin
Leenus
L
Interfakultares Institut fur Biochemie der Universitat Tubingen, Hoppe-Seyler-Strasse 4, D-72076 Tubingen, Germany. lee_casmir@yahoo.com
D001549:Benzamides / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D004261:DNA Replication / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D012093:Replicon / Q000187:drug effects; D013936:Thymidine / Q000378:metabolism
C120227:2-(2-chloro-4-iodophenylamino)-N-cyclopropylmethoxy-3,4-difluorobenzamide; D001549:Benzamides; D013936:Thymidine