Genotoxicity, cytotoxicity and gene expression in patients undergoing elective surgery under isoflurane anaesthesia.
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.
Department of Pathology, UNESP - Univ Estadual Paulista, 18618-970, Botucatu-São Paulo, Brasil. mgbraz@hotmail.com
Mariana Gobbo
MG
Braz
Marina Ázer
MÁ
Mazoti
Juliana
J
Giacobino
Leandro Gobbo
LG
Braz
Márjorie de Assis
Mde A
Golim
Adriana Camargo
AC
Ferrasi
Lídia Raquel
LR
de Carvalho
José Reinaldo Cerqueira
JR
Braz
Daisy Maria Fávero
DM
Salvadori
D018685:Anesthetics, Inhalation / Q000009:adverse effects*; D017209:Apoptosis / Q000187:drug effects*; D001938:Brazil; D020552:Comet Assay; D004249:DNA Damage / Q000235:genetics*; D045647:DNA Glycosylases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D017558:Elective Surgical Procedures; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007530:Isoflurane / Q000009:adverse effects*; D008214:Lymphocytes / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018709:Statistics, Nonparametric; D000076105:X-ray Repair Cross Complementing Protein 1
D018685:Anesthetics, Inhalation; D004268:DNA-Binding Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D007530:Isoflurane; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human
Turk Kardiyol Dern Ars. 2008 Jun;36(4):231-8
18765966
Anesth Analg. 2006 May;102(5):1573-7
16632845
Arch Surg. 2001 Oct;136(10):1190-6
11585514
Ann Surg. 1996 Apr;223(4):434-40
8633923
Mutat Res. 2001 Aug 9;486(3):207-16
11459633
Anaesthesia. 2008 Aug;63(8):861-4
18540930
Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):1122-6
8430083
Adv Exp Med Biol. 1991;283:157-64
2068983
Int J Radiat Oncol Biol Phys. 2006 Oct 1;66(2):537-45
16965996
Br J Anaesth. 1999 Feb;82(2):268-70
10365006
Mutat Res. 1999 Feb 19;439(2):199-206
10023059
J Appl Genet. 2004;45(3):369-74
15306730
Eur J Anaesthesiol. 2005 Aug;22(8):616-23
16119599
Nutr Rev. 1994 Aug;52(8 Pt 1):253-65
7970288
Surgery. 1975 Sep;78(3):363-72
1098195
Coron Artery Dis. 2002 Aug;13(5):269-74
12394651
IARC Monogr Eval Carcinog Risks Hum Suppl. 1987;7:1-440
3482203
J Med. 1987;18(1):55-60
3474342
Mutat Res. 2002 Aug 26;519(1-2):93-101
12160895
Anesthesiology. 2008 Feb;108(2):251-60
18212570
Best Pract Res Clin Anaesthesiol. 2004 Sep;18(3):439-54
15212338
Mutagenesis. 2003 Sep;18(5):423-8
12960410
Ann N Y Acad Sci. 1998 Nov 20;854:23-36
9928417
Anesthesiology. 2004 Sep;101(3):703-9
15329595
Mutat Res. 1998 Sep 25;418(1):1-6
9748475
Br J Anaesth. 1984 Jun;56(6):559-64
6721966
Toxicology. 2006 Mar 15;220(2-3):169-78
16442689
Eur J Anaesthesiol. 2009 Aug;26(8):654-60
19593899
Anesthesiology. 1985 Mar;62(3):305-9
2858171
Toxicol In Vitro. 2007 Aug;21(5):972-6
17412554
Anesthesiology. 1977 May;46(5):346-50
15474
Anesthesiology. 2005 Nov;103(5):1006-14
16249675
Lancet. 1980 Feb 9;1(8163):283-4
6101739
Anesthesiology. 1979 May;50(5):426-30
453561
Pharmacol Res. 2009 Jul;60(1):1-17
19427580
Mutat Res. 2001 May 31;492(1-2):99-107
11377249
Mol Aspects Med. 2007 Jun-Aug;28(3-4):258-75
17628657
Int J Hyg Environ Health. 2009 Jan;212(1):11-7
18023252
Int Arch Occup Environ Health. 2005 Feb;78(1):60-4
15703947
Mutat Res. 2009 Jun 18;666(1-2):39-43
19439331
Arch Surg. 2000 Oct;135(10):1141-7
11030869
Acta Anaesthesiol Scand. 2006 Nov;50(10):1229-37
16978161
Exp Cell Res. 1988 Mar;175(1):184-91
3345800
Anesthesiology. 2001 Dec;95(6):1467-72
11748407
Cell Biol Toxicol. 2009 Feb;25(1):65-71
18038185
Methods. 2001 Dec;25(4):402-8
11846609
Clin Exp Immunol. 1974 Sep;18(1):73-9
4469228
EMBO J. 1996 Dec 2;15(23):6662-70
8978692
Cytometry. 1998 Jan 1;31(1):1-9
9450519
Anesthesiology. 1994 Apr;80(4):906-22
8024145
Mol Cell Biol. 1990 Dec;10(12):6160-71
2247054