title: Lymphocyte DNA damage precedes DNA repair or cell death after orthopaedic surgery under general anaesthesia.
abstract: Anaesthetics have gained a lot of attention for their potential mutagenic/carcinogenic effects. In the present study we have investigated the genotoxicity of the inhalation anaesthetic sevoflurane on DNA of lymphocytes isolated from 20 patients undergoing orthopaedic surgery. The genotoxicity of the anaesthetic was studied by assaying DNA damage, apoptosis, DNA repair enzyme activity and GSH content in peripheral lymphocytes before, 15 min after anaesthesia and 24 h after surgery. Lymphocytes isolated 15 min after anaesthesia showed an increase in oxidized purine and pyrimidine bases without DNA strand break formation. DNA strand breaks occurred on the first post-operative day, associated with an enhancement of DNA repair activity and a decrease in GSH. Formation of strand breaks could be the consequence of DNA repair activity. In fact, at 24 h after surgery most of the oxidized DNA bases were repaired. When DNA damage was not repaired, activation of the cell cycle checkpoint protein p53 could lead to apoptosis. An altered redox status may contribute to lymphocytopenia due to an apoptotic event as a consequence of surgical trauma. The presence of apoptotic cells at 1 day after surgery could support the hypothesis that highly damaged peripheral lymphocytes are committed to undergo programmed cell death if the damage is not repaired. In conclusion, the actual risk from anaesthesia is presumably extremely small. However, these findings contribute to our understanding of the regulation of DNA damage/repair and cell death.
authors.affiliation: Department of Anaesthesiology, Rizzoli Orthopaedic Institute, Via Pupilli, 40136 Bologna, Italy. renalle@libero.it
authors.forename: Renata
authors.initials: R
authors.lastname: Alleva
authors.forename: Marco
authors.initials: M
authors.lastname: Tomasetti
authors.forename: Maria D
authors.initials: MD
authors.lastname: Solenghi
authors.forename: Francesca
authors.initials: F
authors.lastname: Stagni
authors.forename: Flavio
authors.initials: F
authors.lastname: Gamberini
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bassi
authors.forename: Pier Maria
authors.initials: PM
authors.lastname: Fornasari
authors.forename: Guido
authors.initials: G
authors.lastname: Fanelli
authors.forename: Battista
authors.initials: B
authors.lastname: Borghi
mesh_terms: D000328:Adult; D000768:Anesthesia, General / Q000009:adverse effects*; D018685:Anesthetics, Inhalation / Q000009:adverse effects; D016923:Cell Death / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage; D004260:DNA Repair; D004277:DNA, Single-Stranded / Q000187:drug effects; D005260:Female; D005978:Glutathione / Q000032:analysis / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000473:pathology* / Q000502:physiology; D008297:Male; D008738:Methyl Ethers / Q000009:adverse effects; D008875:Middle Aged; D009985:Orthopedics; D018384:Oxidative Stress; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D004277:DNA, Single-Stranded; D008738:Methyl Ethers; D000077149:Sevoflurane; D005978:Glutathione