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Genotoxic effect of combined treatment with anaesthetic sevoflurane and 2 Gy radiation in mice

During intraoperative radiotherapy or brachytherapy, general anesthesia is occasionally used not only for the patients ease of pain but also to calm and ease the psychological pain in very anxious or young patients and also to localize as much as possible the target area and lower the possibility of side effects or repeated unnecessary procedure. Given the fact that ionizing radiation (IR) is a known genotoxic and cytotoxic agent, exposure, the dose and number of IR exposures should be kept at a minimum and volatile anesthetics (VA), as the most used type of general anesthesia can be of great help in that mission. Mechanisms of VA action are enhancing inhibitory postsynaptic channel activity, nicotinic acetylcholine, serotonin, and glutamate in the central nervous system. They are considered generally safe for the patients, but there are studies demonstrating different side effects among patients but also among occupationally exposed personnel. Since there is no study comparing the DNA damage effect from the VA exposure combined with the fractionated single IR dose exposure, we wanted to investigate whether there is a difference in DNA damage response of white blood, kidney, brain, and liver cells in vivo. After gaining all ethical approvals, we anesthetized Swiss albino male mice (60±5 days old, 20-25g body weight) with 2.4% sevoflurane mixture with oxygen and air (50:50) for 2 hours, exposed a group of the 20 animals to 2 Gy IR (60Co, Theratron Phoenix teletherapy unit, Atomic Energy Ltd, dose rate of 1.88 Gy/min), while the other groups were control (non-treated), exposed to only sevoflurane or exposed to only IR. Sevoflurane was chosen as one of the most used VA. Samples of in total 80 animals were taken after 0, 2, 6, and 24 hours from the exposure (5 animals for each time point), and damage was assessed by the alkaline comet assay and Comet Assay IV software (Instem UK) using parameters of comet tail length, tail intensity and tail moment. On the samples prepared in duplicate per each animal and time point, in total 100 comets were analyzed. The cellular DNA repair index was calculated to quantify the cells’ DNA repairing damage efficiency. In white blood cells and the brain, sevoflurane demonstrated a slightly protective effect in combined exposure compared to only IR samples that demonstrated significantly higher damage than control. Kidney and liver demonstrated a delay in initiation of DNA repair processes of 6 hours. The significantly higher values in liver and kidney especially 24 hours from the combined exposure, call for further investigation on the mechanisms of combined VA and IR treatment, with longer time periods of observation than the 24 hours from our study, in order to be sure to what extent the DNA damage remains, and how well the cells can recover from single dose exposure to both agents.

sevoflurane, Swiss albino mice, ionizing radiation, alkaline comet assay

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