The Genotoxic and Cytotoxic Effects of Polystyrene Polymers Doped with Boron and Coumarin Derviatives

Abstract

Objective: A series polymer of polystyrene (PS), which doped with potassium biborate (PS-K₂B₄O₇) and 7-hydroxy-4-methylcoumarin (PS-7H4MC) was prepared by solvent casting method.

Material and Methods: All polymeric materials were characterized by Fourier transform infrared spectroscopy (FTIR). Besides, the molecular optimization of polymeric materials was determined using density functional theory (DFT) in ground state. To predict the reactive regions of polymeric materials, the molecular electrostatic potential (MEP) was investigated using theoretical calculations. Cytotoxicity potentials of different concentrations (0 to 320 mg/L) of metabolites on the cultured human blood cells were determined via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) analyses. In addition, chromosomal aberrations (CA) and micronuclei (MN) tests were scored as genetic endpoints.

Results: The FTIR analysis confirmed the presence of polystyrene polymers dopping with potassium biborate and 7-hydroxy-4-methylcoumarin. The MEP maps showed that the negative potential sites were on oxygen atoms.  The results of MTT and LDH analysis showed that PS-K₂B₄O₇ and PS-7H4MC caused significant decreases of cell viability in a clear dose dependent manner.  

Conclusion: cytogenetic results of this study revealed that these polymers neither induced CA nor MN formations. Potassium biborate and 7-hydroxy-4-methylcoumarin doped polystyrene polymers demonstrated ameliorative potential against toxic effects by PS on cultured human peripheral blood lymphocytes in our experimental conditions.

Keywords

• Polystyrene,coumarin; potassium biborate; DFT; MEP; DNA damage,human blood cells

The Genotoxic and Cytotoxic Effects of Polystyrene Polymers Doped with Boron and Coumarin Derivatives

Öz

References

1. M. Nakai, M. Tsubokura, M. Suzuki, S. Fujishima, Y. Watanabe, Y. Hasegawa and S. Ogura. Genotoxicity of styrene oligomers extracted from polystyrene intended for use in contact with food. Toxicology Reports, 1 (2014)1175-1180.
2. T. Fadida, Y. Kroupitski, U. M.Peiper, T. Bendikov, S. Sela, and E. Poverenov. Air-ozonolysis to generate contact active antimicrobial surfaces: Activation of polyethylene and polystyrene followed by covalent graft of quaternary ammonium salts.” Colloids and Surfaces B: Biointerfaces, 122 (2014) 294-300.
3. L. M. Henderson and G. Speit. Review of the genotoxicity of styrene in humans. Mutation Research/Reviews in Mutation Research, 589 (2005) 158-191.
4. M. Pansuriya, , M. M. Savant, C. V. Bhuva, J. Singh, N. Kapuriya and Y.T. Naliapara. Construction of 3, 4-dihydro-1, 2-diazete ring through 4π electron cyclization of 4-hydroxy-2-oxo-2H chromene-3-carbaldehyde [(1E)-arylmethylene] hydrazone. Journal of Heterocyclic Chemistry, 47 (2010)513-516.
5. S. Sebastian, S. Sylvestre, D. Jayarajan, M. Amalanathan, K. Oudayakumar, T. Gnanapoongothai and T. Jayavarthanan. Molecular structure, Normal Coordinate Analysis, harmonic vibrational frequencies, Natural Bond Orbital, TD-DFT calculations and biological activity analysis of antioxidant drug 7-hydroxycoumarin.” Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 101(2013) 370-381.
6. D. W. Fink and W. R. Koehler. pH effects on fluorescence of umbelliferone.” Analytical Chemistry, 42 (1970) 990-993.
7. C. V. Shank, A. Dienes, A. M. Trozzolo and J.A. Myer. Near UV to yellow tunable laser emission from an organic dye.” Applied Physics Letters, 16 (1970)405-407.
8. Dienes, C.V. Shank and A.M. Trozzolo. Evidence for exciplex laser action in coumarin dyes by measurements of stimulated fluorescence. Applied Physics Letters, 17 (1970) 189-191.

9. K. H. Drexhage. Structure and properties of laser dyes. In Dye lasers (pp. 144-193). Springer Berlin Heidelberg.1973.
10. B. S. Creaven, D. A. Egan, D. Karcz, K. Kavanagh, M. McCann, M. Mahon and M. Walsh. Synthesis, characterisation and antimicrobial activity of copper (II) and manganese (II) complexes of coumarin-6, 7-dioxyacetic acid (cdoaH 2) and 4-methylcoumarin-6, 7-dioxyacetic acid (4-MecdoaH 2): X-ray crystal structures of [Cu (cdoa)(phen) 2]· 8.8 H 2 O and [Cu (4-Mecdoa)(phen) 2]· 13H 2 O (phen= 1, 10-phenanthroline).” Journal of inorganic biochemistry, 101 (2007) 1108-1119.
11. D. S. D. A. Chaves, S. S. Costa, A. P. D. Almeida, F. Frattani, M. Assafim and Zingali, R. B. Secondary metabolites from vegetal origin: a potential source of antithrombotic drugs. Química Nova, 33 (2010) 172-180.
12. F. Chimenti, B. Bizzarri, A. Bolasco, D. Secci, P. Chimenti, A. Granese and F. Sisto. Synthesis, selective anti-Helicobacter pylori activity, and cytotoxicity of novel N-substituted-2-oxo-2H-1-benzopyran-3-carboxamides. Bioorganic & medicinal chemistry letters, 20 (2010) 4922-4926.
13. G. Morabito, D.Trombetta, K. S. Brajendra, , K. P. Ashok, S. P. Virinder, C. Naccari, and L.Saso. Antioxidant properties of 4-methylcoumarins in in vitro cell-free systems. Biochimie, 92 (2010) 1101-1107.
14. M. Kawase, H. Sakagami, N. Motohasni, H. Hauer, S. S. Chatterjee, G. Spengler and J. Molnar, 2005. Coumarin derivatives with tumor-specific cytotoxicity and multidrug resistance reversal activity. In vivo, 19 (2005) 705-711.
15. M. T. Gallardo-Williams, R. E. Chapin, P. E. King, G. J. Moser, T. L. Goldsworthy, J. P. Morrison, R. R. Maronpot. Boron supplementation inhibits the growth and local expression of IGF-1 in human prostate adenocarcinoma (LNCaP) tumors in nude mice. Toxicologic pathology, 32 (2004), 73-78.
16. W. T. Barranco, C. D. Eckhert. Cellular changes in boric acid-treated DU-145 prostate cancer cells. British journal of cancer, 94(2006), 884-890.
17. F. Ç. Çelikezen, H. Turkez, B. Togar, and M. S. Izgi, DNA damaging and biochemical effects of potassium tetraborate. EXCLI journal, 13(2014) 446-450.
18. M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. and et al. Gaussian, Inc., Wallingford CT, 2010.
19. R. Dennington, T. Keith and J. Millam, GaussView, Version 5, Semichem Inc., Shawnee Mission KS, 2010.
20. H. J. Evans, M. L. O'Riordan. Human peripheral blood lymphocytes for the analysis of chromosome aberrations in mutagen tests. Mutation Research/Environmental Mutagenesis and Related Subjects, 31(1975), 135-148.
21. H. Turkez, T. Sisman. Anti-genotoxic effect of hydrated sodium calcium aluminosilicate on genotoxicity to human lymphocytes induced by aflatoxin B1. Toxicology and Industrial Health, 23 (2007) 83-89.
22. F. Ç. Çelikezen, H. Türkez, B. Toğar. In vitro assessment of genotoxic and oxidative effects of zinc borate. Toxicological & Environmental Chemistry, 96 (2014), 777-782.
23. V. Lewerenz, S. Hanelt, C. Nastevska, C. El-Bahay, E. Röhrdanz, R. Kahl. Antioxidants protect primary rat hepatocyte cultures against acetaminophen-induced DNA strand breaks but not against acetaminophen-induced cytotoxicity. Toxicology, 191(2003), 179-187.
24. H. Wang, Y. Xiao, L. Fu, Zhao, H., Zhang, Y., Wan, X., ... Li, X. High-level expression and purification of soluble recombinant FGF21 protein by SUMO fusion in Escherichia coli. BMC biotechnology, 10(2010), 1.
25. S. M.Hussain, K. L. Hess, Gearhart, J. M., Geiss, K. T., Schlager, J. J. In vitro toxicity of nanoparticles in BRL 3A rat liver cells. Toxicology in vitro, 19(2005), 975-983.
26. M. Fenech, A.A. Morley. Measurement of micronuclei in lymphocytes. Mutatin Research, 147 (1985) 29–36.
27. E. I. Kamitsos, Patsis, A. P., Karakassides, M. A. and Chryssikos, G. D. Infrared reflectance spectra of lithium borate glasses. Journal of Non-Crystalline Solids, 126 (1990) 52–67.
28. E. Scrocco, J. Tomasi. Interpretation by means of electrostatic molecular potentials. “ Advances in quantum chemistry, 11 (1979) 115.
29. J.S. Murray, K. Sen. Molecular Electrostatic Potentials, Concepts and Applications. Elsevier, Amsterdam, 1996.
30. F. Akman. Spectroscopic investigation, HOMO–LUMO energies, natural bond orbital (NBO) analysis and thermodynamic properties of two-armed macroinitiator containing coumarin with DFT quantum chemical calculations.” Canadian Journal of Physics, 94 (2016) 1-11.
31. Matsuoka, A. Önfelt, Matsuda, Y., Isama, K., Sakoda, H., Kato, R. and Niimi, S. [Polyploidy induction by spherical size standard polystyrene particles in a Chinese hamster cell line CHL]. Kokuritsu Iyakuhin Shokuhin Eisei Kenkyujo hokoku= Bulletin of National Institute of Health Sciences, 133 (2014) 29-36.
32. K. Min, D. G. Hyun, Jeong, S. Y., Kim, Y. H., Ma, E. S., & Woo, M. H. A new cytotoxic coumarin, 7-[(E)-3′, 7′-dimethyl-6′-oxo-2′, 7′-octadienyl] oxy coumarin, from the leaves of Zanthoxylum schinifolium. Archives of pharmacal research, 34(2011), 723-726.
33. M. Chougala, S. L. Shastri, Holiyachi, M., Shastri, L. A., More, S. S., Ramesh, K. V. Synthesis, anti-microbial and anti-cancer evaluation study of 3-(3-benzofuranyl)-coumarin derivatives. Medicinal Chemistry Research, 24(2015), 4128-4138.
34. D.R. Ilić, V.V. Jevtić, G.P. Radić, K. Arsikin, B. Ristić, L. Harhaji-Trajković, N. Vuković, S. Sukdolak, O. Klisurić, V. Trajković, S.R. Trifunović Eur. J. Med. Chem., 74 (2014), 502–508
35. NTP (National Toxicology Program), 1993. Toxicology and Carcinogenic Studies of Coumarin (CAS No. 91-64-5) in F344/N Rats and B6C3F1Mice (Gavage Studies). Technical Report Series No. 422. NIH Publication No. 92-31153, US Department of Health and Human services, Bethesda, MD.
36. B.G. Lake.Coumarin metabolism, toxicity and carcinogenicity: relevance for human risk assessment. ” (Review) Food and Chemical Toxicology 37 (1999) 423–453.
37. M. Grifoll, A. M. Solanas, J. M. Bayona. Characterization of genotoxic components in sediments by mass spectrometric techniques combined withSalmonella/microsome test.” Archives of environmental contamination and toxicology, 19 (1990) 175-184.
38. Y. Sasaki, Imanishi, H., Ohta, T. and Shirasu, Y. Effects of antimutagenic flavourings on SCEs induced by chemical mutagens in cultured Chinese hamster cells.” Mutation Research/Genetic Toxicology, 189 (1987) 313-318.
39. Fleig, A. M.Thiess. Mutagenicity study of workers employed in the styrene and polystyrene processing and manufacturing industry. Scandinavian journal of work, environment & health, 4(1978) 254-258.
40. R.Tomanin, C. Ballarin, Bartolucci, G. B., De Rosa, E., Sessa, G., Cupiraggi, A. R. and Sarto, F. Chromosome aberrations and micronuclei in lymphocytes of workers exposed to low and medium levels of styrene.” International archives of occupational and environmental health, 64 (1992) 209-215.
41. H. Turkez, Geyikoğlu, F., Dirican, E., Tatar A. “In vitro studies on chemoprotective effect of borax against aflatoxin B1-induced genetic damage in human lymphocytes.” Cytotechnology, 64(2012a):607-12.
42. H.Turkez, F. Geyikoglu. Boric acid: a potential chemoprotective agent against aflatoxin b(1) toxicity in human blood. ” Cytotechnology, 62(2010):157-65.
43. H.Turkez, F. Geyikoglu, A.Tatar, M.S. Keles, I. Kaplan The effects of some boron compounds against heavy metal toxicity in human blood.” Experimental Toxicology Pathology, 64(2012b)93-101.