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Inhibitory effects of paracetamol on DNA repair in mammalian cells

G Brunborg1, J A Holme, J K Hongslo

  • 1Department of Environmental Medicine, National Institute of Public Health, Oslo, Norway.

Mutation Research
|April 1, 1995
PubMed

Insights

Paracetamol may harm DNA repair by inhibiting nucleotide synthesis. Studies show it increases DNA breaks during repair in various cells, suggesting a genotoxic mechanism in humans.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Toxicology

Background:

  • Paracetamol is known to inhibit deoxyribonucleotide (dNTP) synthesis, which is crucial for DNA replication.
  • This inhibition raises concerns about paracetamol's potential to interfere with DNA repair mechanisms.

Purpose of the Study:

  • To investigate the effect of paracetamol on DNA repair in various mammalian cell types.
  • To determine if paracetamol interferes with the repair of DNA damage induced by genotoxic agents.

Main Methods:

  • Mammalian cells were exposed to genotoxic agents (4-nitroquinoline N-oxide, UV-C, MMS, X-rays) and allowed to repair in the presence or absence of paracetamol.
  • Alkaline elution was used to quantify DNA single-strand breaks (SSBs) plus alkali-labile sites.

Main Results:

  • Paracetamol increased DNA SSBs during repair after exposure to 4-nitroquinoline N-oxide and UV-C in multiple cell types.
  • These effects were reversed by deoxyribonucleosides and were not observed with MMS or X-ray-induced damage.
  • Paracetamol elevated transient SSBs during UV repair, particularly in human mononuclear blood cells, without significantly reducing overall photodamage removal.

Conclusions:

  • Paracetamol interferes with nucleotide excision repair in several mammalian cell types.
  • This interference represents a potential mechanism contributing to paracetamol's genotoxicity in humans.

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