Effect of N-hydroxyparacetamol on cell cycle progression.
N-hydroxyparacetamol treatment of rat kidney cells gave rise to a dose-dependent decrease in DNA synthesis. A concentration of 1.0 mM N-hydroxyparacetamol at pH 7.2 decreased the level of DNA synthesis to 13.0 +/- 2.3% of the control value after 1 hr incubation. This compound also caused a perturbation of cell cycle progression. A concentration of 0.44 mM N-hydroxyparacetamol induced G1/S and S phase blocks. These delays became evident at approximately 12 hr after treatment and persisted until about 15 hr when cells started to recover. It seems unlikely that N-hydroxyparacetamol inhibits DNA synthesis and perturbs cycle progression through alterations to DNA structure as such, since this compound failed to alter the migration pattern of naked plasmid DNA.
D000082:Acetaminophen / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000166:cytology; D009690:Nucleic Acid Conformation / Q000187:drug effects; D051381:Rats; D013997:Time Factors
D000082:Acetaminophen; C017372:N-hydroxyacetaminophen