Genotoxicity, Cytotoxicity and Gene Expression in Patients Undergoing Elective Surgery Under Isoflurane Anaesthesia

Overview

Journal Mutagenesis

Publisher Oxford University Press

Specialties Environmental Health
Genetics

Date 2011 Jan 25

PMID 21257718

Citations 7

Authors

Mariana Gobbo Braz

Marina Azer Mazoti

Juliana Giacobino

Leandro Gobbo Braz

Marjorie de Assis Golim

Adriana Camargo Ferrasi

Lidia Raquel de Carvalho

Jose Reinaldo Cerqueira Braz

Daisy Maria Favero Salvadori

Affiliations

Soon will be listed here.

Abstract

There are numerous studies reporting on the effects of inhalation anaesthesia in cells of exposed individuals but not much is known about the ability of isoflurane (ISF) to induce oxidative DNA damage. However, surgery is often associated with a temporary perioperative immunological alteration, and some volatile anaesthetics seem to contribute to a transient lymphocytopenia after surgery. We conducted a study to evaluate a possible genotoxic effect, including oxidative DNA damage, and apoptosis in peripheral lymphocytes of 20 patients American Society of Anaesthesiologists physical status I undergoing minor elective surgery lasting at least 120 min, under anaesthesia with ISF. We also investigated the expression of several genes in blood cells. Blood samples were collected at three time points: before anaesthesia (T(1)), 2 h after the beginning of anaesthesia (T(2)) and on the first post-operative day (T(3)). General DNA damage and oxidised bases (Fpg and endo III-sites) in blood lymphocytes were evaluated using the comet assay. Lymphocytes were phenotyped and apoptosis was evaluated by flow cytometry. In addition, expressions of hOGG1 and XRCC1, genes involved in DNA repair, and BCL2, a gene related to apoptosis, were assessed by quantitative real-time polymerase chain reaction. Results showed no statistically significant difference in the level of DNA damage and oxidised bases among the three sampling times. Anaesthesia with ISF did not increase the percentage of cells in early or late apoptosis in cytotoxic or helper T lymphocytes. Lower hOGG1 and BCL2 expressions were detected at T(3) in comparison to the other two previous time points, and there was significantly lower expression of XRCC1 at T(3) in relation to T(2). In conclusion, the exposure to ISF did not result in genotoxicity and cytotoxicity in lymphocytes and in toxicogenomic effect in leukocytes, although DNA repair and apoptosis-related genes were down-regulated on the first post-operative day.

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References

Yildiz A, Gur M, Yilmaz R, Demirbag R, Celik H, Aslan M . Lymphocyte DNA damage and total antioxidant status in patients with white-coat hypertension and sustained hypertension. Turk Kardiyol Dern Ars. 2008; 36(4):231-8. View

Eroglu A, Celep F, Erciyes N . A comparison of sister chromatid exchanges in lymphocytes of anesthesiologists to nonanesthesiologists in the same hospital. Anesth Analg. 2006; 102(5):1573-7. DOI: 10.1213/01.ane.0000204298.42159.0e. View

Delogu G, Moretti S, Famularo G, Marcellini S, Santini G, Antonucci A . Mitochondrial perturbations and oxidant stress in lymphocytes from patients undergoing surgery and general anesthesia. Arch Surg. 2001; 136(10):1190-6. DOI: 10.1001/archsurg.136.10.1190. View

Oka M, Hirazawa K, Yamamoto K, Iizuka N, Hazama S, Suzuki T . Induction of Fas-mediated apoptosis on circulating lymphocytes by surgical stress. Ann Surg. 1996; 223(4):434-40. PMC: 1235140. DOI: 10.1097/00000658-199604000-00013. View

Janssen K, Schlink K, Gotte W, Hippler B, Kaina B, Oesch F . DNA repair activity of 8-oxoguanine DNA glycosylase 1 (OGG1) in human lymphocytes is not dependent on genetic polymorphism Ser326/Cys326. Mutat Res. 2001; 486(3):207-16. DOI: 10.1016/s0921-8777(01)00096-9. View

Wiesner G, Schiewe-Langgartner F, Lindner R, Gruber M . Increased formation of sister chromatid exchanges, but not of micronuclei, in anaesthetists exposed to low levels of sevoflurane. Anaesthesia. 2008; 63(8):861-4. DOI: 10.1111/j.1365-2044.2008.05498.x. View

Moriya M . Single-stranded shuttle phagemid for mutagenesis studies in mammalian cells: 8-oxoguanine in DNA induces targeted G.C-->T.A transversions in simian kidney cells. Proc Natl Acad Sci U S A. 1993; 90(3):1122-6. PMC: 45823. DOI: 10.1073/pnas.90.3.1122. View

Tice R, Andrews P, Hirai O, Singh N . The single cell gel (SCG) assay: an electrophoretic technique for the detection of DNA damage in individual cells. Adv Exp Med Biol. 1991; 283:157-64. DOI: 10.1007/978-1-4684-5877-0_17. View

Cornetta T, Festa F, Testa A, Cozzi R . DNA damage repair and genetic polymorphisms: assessment of individual sensitivity and repair capacity. Int J Radiat Oncol Biol Phys. 2006; 66(2):537-45. DOI: 10.1016/j.ijrobp.2006.06.037. View

10.

Hoerauf K, Schrogendorfer K, Wiesner G, Gruber M, Spacek A, Kress H . Sister chromatid exchange in human lymphocytes exposed to isoflurane and nitrous oxide in vitro. Br J Anaesth. 1999; 82(2):268-70. DOI: 10.1093/bja/82.2.268. View

11.

Jaloszynski P, Kujawski M, Wasowicz M, Szulc R, Szyfter K . Genotoxicity of inhalation anesthetics halothane and isoflurane in human lymphocytes studied in vitro using the comet assay. Mutat Res. 1999; 439(2):199-206. DOI: 10.1016/s1383-5718(98)00195-8. View

12.

Szyfter K, Szulc R, Mikstacki A, Stachecki I, Rydzanicz M, Jaloszynski P . Genotoxicity of inhalation anaesthetics: DNA lesions generated by sevoflurane in vitro and in vivo. J Appl Genet. 2004; 45(3):369-74. View

13.

Schneemilch C, Hachenberg T, Ansorge S, Ittenson A, Bank U . Effects of different anaesthetic agents on immune cell function in vitro. Eur J Anaesthesiol. 2005; 22(8):616-23. DOI: 10.1017/s0265021505001031. View

14.

Halliwell B . Free radicals and antioxidants: a personal view. Nutr Rev. 1994; 52(8 Pt 1):253-65. DOI: 10.1111/j.1753-4887.1994.tb01453.x. View

15.

Slade M, Simmons R, Yunis E, Greenberg L . Immunodepression after major surgery in normal patients. Surgery. 1975; 78(3):363-72. View

16.

Botto N, Masetti S, Petrozzi L, Vassalle C, Manfredi S, Biagini A . Elevated levels of oxidative DNA damage in patients with coronary artery disease. Coron Artery Dis. 2002; 13(5):269-74. DOI: 10.1097/00019501-200208000-00004. View

17.

. Overall evaluations of carcinogenicity: an updating of IARC Monographs volumes 1 to 42. IARC Monogr Eval Carcinog Risks Hum Suppl. 1987; 7:1-440. View

18.

TRUDNOWSKI R, Mehta M, Rucinski M . Evaluation of the mutagenic potential of enflurane and isoflurane by sister chromatid exchange. J Med. 1987; 18(1):55-60. View

19.

Lei Y, Chang C, Kuo H, Luo J, Chang M, Cheng T . Effects on sister chromatid exchange frequency of polymorphisms in DNA repair gene XRCC1 in smokers. Mutat Res. 2002; 519(1-2):93-101. DOI: 10.1016/s1383-5718(02)00127-4. View

20.

Wei H, Liang G, Yang H, Wang Q, Hawkins B, Madesh M . The common inhalational anesthetic isoflurane induces apoptosis via activation of inositol 1,4,5-trisphosphate receptors. Anesthesiology. 2008; 108(2):251-60. DOI: 10.1097/01.anes.0000299435.59242.0e. View