Kidney cell DNA damage caused by combined exposure to volatile anaesthetics and 1 Gy or 2 Gy radiotherapy dose in vivo

  • Vesna Benković Faculty of Science, University of Zagreb, Zagreb
  • Nada Oršolić Department of Biology, Faculty of Science, University of Zagreb,
  • Anica Horvat Knežević Department of Biology, Faculty of Science, University of Zagreb,
  • Nikola Borojević Warrington and Halton Teaching Hospitals NHS Foundation Trust, Lovely Ln, Warrington WA5 1QG, United Kingdom
  • Gordana Brozović Department of Anaesthesiology, Reanimatology and ICU, University Hospital for Tumours, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia
  • Mirta Milić Institute for Medical Research and Occupational Health, Mutagenesis Unit Zagreb, Croatia
Keywords: DNA repair index, comet assay, halothane, isoflurane, sevoflurane, tail intensity, tail length

Abstract

Patient immobilisation with volatile anaesthetics (VA) during radiotherapy is sometimes unavoidable. Although it is known that both VAs and ionising radiation can have nephrotoxic effects, there are no studies of their combined effects on DNA damage. The aim of this in vivo study was to address this gap by investigating whether 48 groups of healthy Swiss albino mice (totalling 240) would differ in kidney cell DNA damage response (alkaline comet assay) to isoflurane, sevoflurane, or halothane anaesthesia and exposure to 1 Gy or 2 Gy of ionising radiation. We took kidney cortex samples after 0, 2, 6, and 24 h of exposure and measured comet parameters: tail length and tail intensity. To quantify the efficiency of the cells to repair and re-join DNA strand breaks, we also calculated cellular DNA repair index. Exposure to either VA alone increased DNA damage, which was similar between sevoflurane and isoflurane, and the highest with halothane. In combined exposure (VA and irradiation with 1 Gy) DNA damage remained at similar levels for all time points or was even lower than damage caused by radiation alone. Halothane again demonstrated the highest damage. In combined exposure with irradiation of 2 Gy sevoflurane significantly elevated tail intensity over the first three time points, which decreased and was even lower on hour 24 than in samples exposed to the corresponding radiation dose alone. This study confirmed that volatile anaesthetics are capable of damaging DNA, while combined VA and 1 Gy or 2 Gy treatment did not have a synergistic damaging effect on DNA. Further studies on the mechanisms of action are needed to determine the extent of damage in kidney cells after longer periods of observation and how efficiently the cells can recover from exposure to single and multiple doses of volatile anaesthetics and radiotherapy.

Published
2022-03-23
How to Cite
1.
Benković V, Oršolić N, Horvat Knežević A, Borojević N, Brozović G, Milić M. Kidney cell DNA damage caused by combined exposure to volatile anaesthetics and 1 Gy or 2 Gy radiotherapy dose in vivo. Arh Hig Rada Toksikol [Internet]. 2022Mar.23 [cited 2022Aug.14];73(1). Available from: https://arhiv.imi.hr/index.php/arhiv/article/view/1449
Section
Original article