Turhan Kadir, Ozturkcan S Arda, Turgut Zuhal, Karadayi Mehmet, Aslan Ali, Gulluce Medine
1Department of Chemistry, Faculty of Science and Art, Yildiz Technical University, Istanbul, Turkey.
Toxicol Ind Health. 2014 Apr;30(3):275-83. doi: 10.1177/0748233712456060. Epub 2012 Aug 17.
The current study aims to determine the genotoxic and antigenotoxic potential of four newly synthesized dihydropyridine derivatives using Escherichia coli WP2 and Ames/Salmonella bacterial reversion assay systems. The bacterial mutant tester strains, E. coli WP2uvrA with a point mutation and Salmonella typhimurium TA1537 with a frameshift mutation, were used to determine genotoxic potentials of the test compounds. To determine antigenotoxic potentials of the test compounds, the same strains were also used together with positive mutagens N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) for E. coli WP2uvrA and 9-aminoacridine (9-AA) for S. typhimurium TA1537. According to the results, neither of the test compounds showed significant genotoxic activity on both tester strains at the tested concentrations. However, except compound 4, all the test compounds showed significant antigenotoxic activity on MNNG- or/and 9-AA-induced mutations. The inhibition rates of mutagenesis ranged from 27.0% (compound 2: 2.5 mM/plate) to 65.0% (compound 2: 0.5 mM/plate) for MNNG and from 30.6% (compound 2: 2 mM/plate) to 58.5% (compound 1: 1 mM/plate) for 9-AA genotoxicity. According to these results, it is concluded that all the test compounds do not have a mutagenic potential on the bacterial strains at the tested concentrations, and some of them have antigenotoxic potentials against MNNG- and 9-AA-induced mutagenesis.
本研究旨在利用大肠杆菌WP2和艾姆斯/沙门氏菌细菌回复突变试验系统,确定四种新合成的二氢吡啶衍生物的遗传毒性和抗遗传毒性潜力。使用具有点突变的细菌突变测试菌株大肠杆菌WP2uvrA和具有移码突变的鼠伤寒沙门氏菌TA1537来确定受试化合物的遗传毒性潜力。为了确定受试化合物的抗遗传毒性潜力,还将相同的菌株与用于大肠杆菌WP2uvrA的阳性诱变剂N-甲基-N'-硝基-N-亚硝基胍(MNNG)和用于鼠伤寒沙门氏菌TA1537的9-氨基吖啶(9-AA)一起使用。根据结果,在测试浓度下,受试化合物在两种测试菌株上均未显示出显著的遗传毒性活性。然而,除化合物4外,所有受试化合物对MNNG或/和9-AA诱导的突变均显示出显著的抗遗传毒性活性。对于MNNG,诱变抑制率范围为27.0%(化合物2:2.5 mM/平板)至65.0%(化合物2:0.5 mM/平板);对于9-AA遗传毒性,诱变抑制率范围为30.6%(化合物2:2 mM/平板)至58.5%(化合物1:1 mM/平板)。根据这些结果,可以得出结论,在测试浓度下,所有受试化合物对细菌菌株均无诱变潜力,其中一些化合物对MNNG和9-AA诱导的诱变具有抗遗传毒性潜力。