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An in vitro study of the potential genotoxicity and cytotoxicity of paracetamol in HepG2 cells using the comet assay and two different cytotoxicity assays
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
2016 (English)Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

Paracetamol is a well-known over-the-counter analgesic that has been used for several decades. Whereas considered safe when taken in therapeutic doses, overdoses have the potential to induce hepatotoxicity. Several studies have reported that paracetamol may also induce genotoxic effects and these findings caused a concern about the safety of paracetamol. Although still assessed as safe by the authorities, the picture of the potential genotoxicity of paracetamol is still quite complex. The aim of this study was to evaluate the potential DNA damaging effects of paracetamol and cyclophosphamide (a well-known genotoxic agent used as a positive control) in a human hepatoma cell line (HepG2) after 24 h of exposure using the alkaline version of the comet assay. An additional aim was to evaluate the cytotoxicity using the MTT assay and the Hoechst staining technique. The result of the present study indicated that 1 mM of paracetamol, using this specific in vitro system and experimental conditions, increases the level of DNA damage. This effect was observed without concomitant cytotoxicity. Interestingly, this finding does not fully support the current regulatory review on the genotoxic effects associated with paracetamol, i.e. that the genotoxic effects observed in previous in vitro studies were commonly associated with concomitant cytotoxicity. However, due to the limitations of this present in vitro study based on HepG2 cells, the obtained results must be interpreted carefully and are most likely not of clinical relevance. Two unexpected findings were the absence of an obvious relationship between the observed level of DNA damage and the concentrations of paracetamol, and that the two assays used for the evaluation of cytotoxicity gave different results. 

Place, publisher, year, edition, pages
2016. , 37 p.
Keyword [en]
paracetamol, cyclophosphamide, HepG2, DNA damage, cytotoxicity, genotoxicity, comet assay, Hoechst staining, MTT assay
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-313833OAI: oai:DiVA.org:uu-313833DiVA: diva2:1068317
Educational program
Master of Science Programme in Pharmacy
Supervisors
Examiners
Available from: 2017-05-09 Created: 2017-01-24 Last updated: 2017-05-09Bibliographically approved

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Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association
  • vancouver
  • Other style
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Language
  • de-DE
  • en-GB
  • en-US
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  • nn-NB
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Output format
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