Iron chelators hydroxyurea and bathophenanthroline disulfonate inhibit DNA synthesis by different pathways.
We previously showed that thrombin-stimulated DNA synthesis in CCL 39 cells was inhibited by hydroxyurea (HU) and bathophenanthroline disulfonate (BPS) (Proc. Natl. Acad. Sci. USA, in press). A clear difference exists between these two inhibitors. Inhibition mediated by HU was immediate and must be present in the culture medium. BPS was equally effective when it was present in the medium or after preincubation, but it required at least 12 h to achieve maximal effect. The permeable form 1,10 phenanthroline had the same inhibitory effect in short-term incubations that BPS. Moreover, 1,10 phenanthroline was cytotoxic in long-term incubations indicating that the site of BPS inhibition was outside the cell. Further, long-term incubations with HU did not affect the ability of the cell to reinitiate DNA synthesis after removal of the chelator.
Departamento de Biología Celular, Universidad de Córdoba, Spain.
F J
FJ
Alcaín
H
H
Löw
F L
FL
Crane
P
P
Navas
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000096:biosynthesis* / Q000187:drug effects; D006918:Hydroxyurea / Q000494:pharmacology*; D007502:Iron Chelating Agents / Q000494:pharmacology*; D007700:Kinetics; D008168:Lung; D010618:Phenanthrolines / Q000494:pharmacology*; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D007502:Iron Chelating Agents; D010618:Phenanthrolines; C017049:bathophenanthroline disulfonic acid; D004247:DNA; D013917:Thrombin; C025205:1,10-phenanthroline; D006918:Hydroxyurea