title: In vitro genotoxicity and cytotoxicity of a particular combination of pemetrexed and cefixime in human peripheral blood lymphocytes.
abstract: This study aims to find the genotoxic and cytotoxic effects of a particular combination of pemetrexed (PMX) and cefixime (CFX) in human peripheral blood lymphocytes. Chromosome aberration (CA), sister chromatid exchange (SCE), and micronucleus (MN) tests were used to assess genotoxicity. Whereas, the cytotoxicity was evaluated by using mitotic index (MI), proliferation index (PI), and nuclear division index (NDI). Our tests were proceeded with concentrations of 12.5 + 450, 25 + 800, 37.5 + 1150, and 50 + 1500 μg/mL of a mixture of PMX and CFX separately for 24 hr and 48 hr. The combination of PMX + CFX did not induce the CA or SCE in human peripheral blood lymphocytes when compared with both the control and the solvent control. MN in human peripheral blood lymphocytes was not significantly increased after treatment with a particular combination of PMX + CFX. However, PMX + CFX significantly decreased the MI, PI and NDI at all concentrations for 24- and 48-hr treatment periods when compared with both controls. Generally, PMX + CFX inhibited cell proliferation more than positive control (MMC) and showed a higher cytotoxic effect than MMC at both treatment periods. These results were compared with individual effects of PMX and CFX. As a result, it was observed that a particular combination of PMX + CFX was not genotoxic. However, the combination synergistically increase cytotoxicity in human peripheral blood lymphocytes.
authors: Department of Biology, Faculty of Science and Letter, Cukurova University, 01330 Adana, Turkey.
authors: Erman Salih
authors: ES
authors: Istifli
authors: Department of Biology, Faculty of Science and Letter, Cukurova University, 01330 Adana, Turkey.
authors: Mehmet
authors: M
authors: Topaktaş
keywords: Cefixime; Cytotoxicity; Genotoxicity; Human peripheral lymphocytes; Pemetrexed; Synergism
references: Int J Oncol. 2012 Jul;41(1):24-30
references: 22552400
references: Cancer Chemother Pharmacol. 1997;39(6):521-31
references: 9118464
references: Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3290-5
references: 9096386
references: Antimicrob Agents Chemother. 1988 Dec;32(12):1848-53
references: 3266730
references: Ann N Y Acad Sci. 2006 Dec;1090:209-16
references: 17384264
references: Pharmacol Rev. 2006 Sep;58(3):621-81
references: 16968952
references: Mutagenesis. 1999 Mar;14(2):221-6
references: 10229925
references: Cell Death Dis. 2014 Feb 06;5:e1045
references: 24503537
references: J Med Chem. 2006 Nov 16;49(23):6819-32
references: 17154512
references: Mol Cancer. 2012 Apr 26;11:25
references: 22537194
references: Lung Cancer. 2010 Feb;67(2):160-5
references: 19450893
references: Environ Health Perspect. 2005 May;113(5):517-20
references: 15866756
references: J Clin Oncol. 2000 Jan;18(2):325-31
references: 10637246
references: Carcinogenesis. 2007 Mar;28(3):625-31
references: 16973674
references: Mutagenesis. 2011 Jan;26(1):239-45
references: 21164208
references: Pediatr Int. 2004 Aug;46(4):415-8
references: 15310305
references: Autophagy. 2011 Oct;7(10):1261-2
references: 21814046
references: Cancer Res. 2000 Jan 15;60(2):390-4
references: 10667592
references: Nature. 1978 Feb 9;271(5645):551-3
references: 622190
references: Environ Mol Mutagen. 2009 Jul;50(6):435-50
references: 19334052
references: Mutat Res. 1975 Jun;31(3):135-48
references: 1128546
references: Environ Health Perspect. 2002 Nov;110(11):1077-80
references: 12417477
references: Mayo Clin Proc. 2008 May;83(5):584-94
references: 18452692
references: Mutat Res. 1978 Nov;52(2):199-206
references: 740006
references: J Antimicrob Chemother. 2006 Jul;58(1):228-30
references: 16717053
references: Ther Drug Monit. 1993 Oct;15(5):375-9
references: 8249043
references: Cancer Res. 2000 Mar 15;60(6):1619-25
references: 10749131
references: Mutat Res. 2000 Aug;463(2):111-72
references: 10913908
references: Cancer Biol Ther. 2012 Jul;13(9):793-803
references: 22673740
references: Mutagenesis. 2011 Jan;26(1):93-100
references: 21164188
references: Chem Res Toxicol. 2013 Aug 19;26(8):1168-81
references: 23848171
references: Acta Pol Pharm. 1992;49(1-2):35-40
references: 8769079
references: Mutat Res. 2003 Oct 7;540(2):153-63
references: 14550499
references: J Med Chem. 2006 Jun 29;49(13):3766-9
references: 16789733
references: Am J Epidemiol. 2007 Jan 1;165(1):36-43
references: 17071846
references: Cancer Genet Cytogenet. 1995 Feb;79(2):133-5
references: 7889505
references: Cancer Res. 1998 Sep 15;58(18):4117-21
references: 9751622
references: Hum Genet. 1985;70(2):126-9
references: 2408987
references: Cancer Chemother Pharmacol. 1988;22(1):26-32
references: 3396144
references: Cancer Res. 1999 Apr 1;59(7):1481-4
references: 10197617
references: Mutat Res. 1988 Mar;204(3):379-406
references: 3347212
references: Mutat Res. 2000 Nov 20;455(1-2):81-95
references: 11113469
references: Cancer Res. 2004 Mar 15;64(6):2258-63
references: 15026371
references: Cancer Res. 1994 Jun 1;54(11):2919-22
references: 8187078
references: Cancer Res. 1984 May;44(5):1913-7
references: 6713392
references: Cancer Res. 1983 Aug;43(8):3511-3
references: 6683123
references: Cytotechnology. 2013 Aug;65(4):621-8
references: 23179091