Inhibition of DNA, RNA and protein synthesis and chromatin alteration by N-hydroxyphenacetin.
The effects of N-hydroxyphenacetin on DNA function and structure were investigated to elucidate the involvement of phenacetin in analgesic nephropathy and transitional cell carcinoma. N-Hydroxyphenacetin or a metabolite inhibited synthesis of DNA, RNA and protein; DNA inhibition was greater at higher pH. No single-strand breaks were detectable in DNA after N-hydroxyphenacetin treatment and no appreciable effect on cell viability was observed at concentrations up to 5 mM. N-Hydroxyphenacetin-induced alteration to chromatin structure was detected using nucleoid sedimentation analysis. Direct binding to plasmid DNA was not observed. These observations are consistent with a role for phenacetin metabolites in renal disease.
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002843:Chromatin / Q000187:drug effects*; D004247:DNA / Q000096:biosynthesis; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced; D010615:Phenacetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis
D002843:Chromatin; C008068:N-hydroxyphenacetin; D012313:RNA; D004247:DNA; D010615:Phenacetin