In vitro assessment of the cytotoxic, DNA damaging, and cytogenetic effects of hydroquinone in human peripheral blood lymphocytes

  • Karlo Jurica Special Security Operations Directorate, Ministry of the Interior
  • Irena Brčić Karačonji Institute for Medical Research and Occupational Health, Zagreb
  • Vesna Benković Faculty of Science, University of Zagreb, Zagreb
  • Nevenka Kopjar Institute for Medical Research and Occupational Health, Zagreb
Keywords: apoptosis, cytokinesis-block micronucleus, nuclear buds, primary DNA damage, total comet area

Abstract

This study investigated the mechanisms of hydroquinone toxicity and assessed the relationships between its cytotoxic, genotoxic, and cytogenetic effects tested at 8, 140, and 280 µg mL-1 in human peripheral blood lymphocytes exposed for 24 h. The outcomes of the treatments were evaluated using the apoptosis/necrosis assay, the alkaline comet assay, and the cytokinesis-block micronucleus (CBMN) cytome assay. The tested hydroquinone concentrations produced relatively weak cytotoxicity in resting lymphocytes, which mostly died via apoptosis. Hydroquinone’s marked genotoxic effects were detected using the alkaline comet assay. Significantly decreased values of all comet parameters compared to controls indicated specific mechanisms of hydroquinone-DNA interactions. Our results suggest that the two higher hydroquinone concentrations possibly led to cross-linking and adduct formation. Increased levels of DNA breakage measured following exposure to the lowest concentration suggested mechanisms related to oxidative stress and inhibition of topoisomerase II. At 8 µg mL-1, hydroquinone did not significantly affect MN formation. At 140 and 280 µg mL-1, it completely blocked lymphocyte division. The two latter concentrations also led to erythrocyte stabilization and prevented their lysis. At least two facts contribute to this study’s relevance: (I) this is the first study that quantifies the degree of reduction in total comet area measured in lymphocyte DNA after hydroquinone treatment, (II) it is also the first one on a lymphocyte model that adopted the “cytome” protocol in an MN assay and found that lymphocytes exposure even to low hydroquinone concentration resulted in a significant increase of nuclear bud frequency. Considering the limitations of the lymphocyte model, which does not possess intrinsic metabolic activation, in order to unequivocally prove the obtained results further studies using other appropriate cell lines are advised.

Published
2017-11-15
How to Cite
1.
Jurica K, Brčić Karačonji I, Benković V, Kopjar N. In vitro assessment of the cytotoxic, DNA damaging, and cytogenetic effects of hydroquinone in human peripheral blood lymphocytes. AIHT [Internet]. 15Nov.2017 [cited 16Aug.2018];68(4). Available from: https://arhiv.imi.hr/index.php/arhiv/article/view/862
Section
Original article