Inhibition of SV40 DNA replication in vitro by chlorpromazine.
We examined the inhibitory effect of chlorpromazine, a phenothiazine derivative, on SV40 DNA replication in a HeLa cell extract. The inhibition by chlorpromazine was reversed by cardiolipin, phosphatidylinositol, phosphatidylglycerol, and phosphatidylserine. Studies on a staged reaction showed that the pre-elongation step was sensitive to chlorpromazine: chlorpromazine-resistant DNA synthesis was observed when the drug was added after the pre-elongation step. Analysis of replication products by agarose gel electrophoresis revealed that some steps of DNA chain elongation and maturation of closed circular forms were also sensitive to this drug.
Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
H
H
Hirai
S
S
Takeda
S
S
Natori
K
K
Sekimizu
D002746:Chlorpromazine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects*; D004279:DNA, Viral / Q000096:biosynthesis*; D004587:Electrophoresis, Agar Gel; D006367:HeLa Cells; D006801:Humans; D010743:Phospholipids / Q000494:pharmacology; D013539:Simian virus 40 / Q000187:drug effects / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects*
D004279:DNA, Viral; D010743:Phospholipids; D002746:Chlorpromazine