PMID: 8600357Feb 1, 1996Paper

Series: current issues in mutagenesis and carcinogenesis, No. 65. The genotoxicity and carcinogenicity of paracetamol: a regulatory (re)view

Mutation Research
K BergmanS W Teigen

Abstract

The publication of several studies reporting genotoxic effects of paracetamol, one of the world's most popular over-the-counter drugs, has raised the question of regulatory action. Paracetamol does not cause gene mutations, either in bacteria or in mammalian cells. There are, however, published data giving clear evidence that paracetamol causes chromosomal damage in vitro in mammalian cells at high concentrations and indicating that similar effects occur in vivo at high dosages. Available data point to three possible mechanisms of paracetamol-induced genotoxicity: (1) inhibition of ribonucleotide reductase; (2) increase in cytosolic and intranuclear Ca2+ levels; (3) DNA damage caused by NAPQI after glutathione depletion. All mechanisms involve dose thresholds. Studies of the relationship between genotoxicity and toxic effects in the rat (induction of micronuclei in rat bone marrow including dose-response relationship, biotransformation of paracetamol at different dosages, concomitant toxicity and biochemical markers) have recently been completed. These studies, which employed doses ranging from the dose resulting in human therapeutic peak plasma levels to highly toxic doses, give convincing evidence that genotoxic effects of pa...Continue Reading

Citations

Oct 22, 2010·Environmental and Molecular Mutagenesis·Kerry L DearfieldKristine L Witt
Mar 19, 2020·Environmental and Molecular Mutagenesis·Bas-Jan van der LeedeJacky Van Gompel
Aug 5, 2000·Human & Experimental Toxicology·P J O'BrienP J Bugelski
Jan 25, 2012·Journal of Toxicologic Pathology·Robert A EttlinDavid E Prentice
May 25, 2012·Carcinogenesis·C MagkoufopoulouJ H M van Delft
Jun 15, 2013·Environmental Science and Pollution Research International·S C AntunesBruno Nunes
Nov 1, 2000·Proceedings of the National Academy of Sciences of the United States of America·C J HendersonB K Park
May 11, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Roland B WalterEmily White
May 28, 2019·Environmental Science and Pollution Research International·Valéria Giménez, Bruno Nunes
Jul 1, 2011·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Julie A RossPhuong L Nguyen
Jan 4, 2021·Regulatory Toxicology and Pharmacology : RTP·Hartmut JaeschkeGary Eichenbaum
Jan 27, 2021·Environmental Science and Pollution Research International·Ana Filipa Nogueira, Bruno Nunes
Jun 3, 2021·Journal of Clinical Medicine·Jesús Prego-Domínguez, Bahi Takkouche

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