Inhibition of DNA, RNA and protein synthesis and chromatin alteration by N-hydroxyphenacetin.

Abstract

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.

• Authors: N K Hayward, M F Lavin
• Journal: Xenobiotica; the fate of foreign compounds in biological systems (Xenobiotica) Vol. 17 Issue 1 Pg. 115-24 (Jan 1987) ISSN: 0049-8254 [Print] England
• PMID: 2435067 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chromatin
• N-hydroxyphenacetin
• RNA
• DNA
• Phenacetin

Topics

• Cell Line
• Cell Survival (drug effects)
• Chromatin (drug effects)
• DNA (biosynthesis)
• DNA Damage
• DNA Repair (drug effects)
• Humans
• Kidney Diseases (chemically induced)
• Phenacetin (analogs & derivatives, pharmacology)
• Protein Biosynthesis
• RNA (biosynthesis)