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The effects of 4-thujanol on chromosome aberrations, sister chromatid exchanges and micronucleus in human peripheral blood lymphocytes

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Abstract

4-Thujanol, a bicyclic monoterpene alcohol, is present in the essential oils of many medicinal and aromatic plants. It is commonly used as a fragrance and flavouring ingredient in a lot of different products. The potential genotoxic effects of 4-thujanol on human peripheral blood lymphocytes (PBLs) were investigated in vitro by the chromosome aberrations (CAs), sister chromatid exchanges (SCEs), and micronucleus (MN) tests. The cells were treated with 13, 26 and 52 μg/mL 4-thujanol in the presence and absence of a metabolic activator (S9 mix). 4-Thujanol induced CA (P < 0.001) and MN formation (P < 0.05) at all concentrations (13, 26 and 52 μg/mL) in the presence and absence of the S9 mix without a concentration-dependent manner. However, the treatment of peripheral lymphocytes with 4-thujanol did not produce a statistical difference in the frequency of SCEs when compared with control group. Furthermore, this monoterpene did not significantly decrease the mitotic index (MI), proliferation index (PI), and nuclear division index (NDI). In conclusion, 4-thujanol had a significant clastogenic effect at the tested concentrations (13, 26 and 52 μg/mL) for human PBLs. In addition, no cytotoxic and/or cytostatic effects were observed regardless of the concentrations used. This work presents the first report on genotoxic properties of 4-thujanol.

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Abbreviations

CA:

Chromosome aberration

SCE:

Sister chromatid exchange

MN:

Micronucleus

PBLs:

Peripheral blood lymphocytes

MNBN:

Micronucleated binuclear cell

MI:

Mitotic index

PI:

Proliferation index

NDI:

Nuclear division index

MMC:

Mitomycin-C

CP:

Cyclophosphamide

Cyt-B:

Cytochalasin B

References

  • Albertini RJ, Anderson D, Douglas GR, Hagmar L, Hemminki K, Merlo F, Natarajan AT, Norppa H, Shuker DEG, Tice R, Waters MD, Aitio A (2000) IPCS guidelines for the monitoring of genotoxic effects of carcinogens in humans. Mutat Res 463:111–172

    Article  CAS  Google Scholar 

  • Al-Kalaldeh JZ, Abu-Dahab R, Afifi FU (2010) Volatile oil composition and antiproliferative activity of Laurus nobilis, Origanum syriacum, Origanum vulgare, and Salvia triloba against human breast adenocarcinoma cells. Nutr Res 30:271–278

    Article  CAS  Google Scholar 

  • Ananthi R, Chandra N, Santhiya ST, Ramesh A (2010) Genotoxic and antigenotoxic effects of Hemidesmus indicus R. Br. root extract in cultured lymphocytes. J Ethnopharmacol 127:558–560

    Article  CAS  Google Scholar 

  • Aydın S, Başaran AA, Başaran N (2005) Modulating effects of thyme and its major ingredients on oxidative DNA damage in human lymphocytes. J Agric Food Chem 53:1299–1305

    Article  Google Scholar 

  • Azirak S, Rencuzogullari E (2008) The in vivo genotoxic effects of carvacrol and thymol in rat bone marrow cells. Environ Toxicol 23:728–735

    Article  CAS  Google Scholar 

  • Bakkali F, Averbeck S, Averbeck D, Idaomar M (2008) Biological effects of essential oils-a review. Food Chem Toxicol 46:446–475

    Article  CAS  Google Scholar 

  • Bhatia SP, Letizia CS, Api AM (2008) Fragrance material review on 4-thujanol. Food Chem Toxicol 46:295–296

    Article  Google Scholar 

  • Bonassi S, Fenech M, Lando C et al (2001) Human micronucleus project: international database comparison for results with the cytokinesis block micronucleus assay in human lymphocytes: effect of laboratory protocol, scoring criteria, and host factors on the frequency of micronuclei. Environ Mol Mutagen 37:31–45

    Article  CAS  Google Scholar 

  • Bonassi S, Znaor A, Ceppi M, Lando C, Chang WP, Holland N, Kirsch-Volders M, Zeiger E, Ban S, Barale R, Bigatti MP, Bolognesi C, Cebulska-Wasilewska A, Fabianova E, Fucic A, Hagmar L, Joksic G, Martelli A, Migliore L, Mirkova E, Scarfi MR, Zijno A, Norppa H, Fenech M (2007) An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans. Carcinogenesis 28:625–631

    Article  CAS  Google Scholar 

  • Buyukleyla M, Rencuzogullari E (2009) The effects of thymol on sister chromatid exchange, chromosome aberration and micronucleus in human lymphocytes. Ecotoxicol Environ Saf 72:943–947

    Article  CAS  Google Scholar 

  • Candan F, Unlü M, Tepe B, Daferera AD, Polissiou M, Sökmen A, Akpulat HA (2003) Antioxidant and antimicrobial activity of essential oil and methanol extracts of Achillea millefolium subsp. Millefolium Afan. (Asteraceae). J Ethnopharmacol 87:215–220

    Article  CAS  Google Scholar 

  • Carrano AV, Natarajan AT (1988) Consideration for population monitoring using cytogenetic techniques. Mutat Res 204:379–406

    Article  CAS  Google Scholar 

  • De Sant’anna JR, Da Silva Franco CC, Miyamoto CT, Cunico MM, Miguel OG, Cocco LC, Yamamoto CI, Junior CC, De Castro-Prado AA (2009) Genotoxicity of Achillea millefolium essential oil in diploid cells of Aspergillus nidulans. Phytother Res 23:231–235

    Article  Google Scholar 

  • Di Sotto A, Mazzanti G, Carbone F, Hrelia P, Maffei F (2010) Inhibition by β-caryophyllene of ethyl methanesulfonate-induced clatogenicity in cultured human lymphocytes. Mutat Res 699:23–28

    CAS  Google Scholar 

  • Eastmond DA, Tucker JD (1989) Identification of aneuploidy-inducing agents using cytokinesis-blocked human lymphocytes and an anti-kinetochore antibody. Environ Mol Mutagen 13:34–43

    Article  CAS  Google Scholar 

  • Eke D, Çelik A (2008) Genotoxicity of thimerosal in cultured human lymphocytes with and without metabolic activation sister chromatid exchange analysis proliferation index and mitotic index. Toxicol In Vitro 22:927–934

    Article  CAS  Google Scholar 

  • Evans HJ (1984) Human peripheral blood lymphocytes for the analysis of chromosome aberrations in mutagen tests. In: Kilbey BJ, Legator M, Nichols W, Ramel C (eds) Handbook of mutagenicity test procedures, 2nd edn. Elsevier Science Publishers BV, Amsterdam, pp 405–427

    Google Scholar 

  • Fenech M (2000) The in vitro micronucleus technique. Mutat Res 455:81–95

    Article  CAS  Google Scholar 

  • Fenech M, Bonassi S (2011) The effect of age, gender, diet and lifestyle on DNA damage measured using micronucleus frequency in human peripheral blood lymphocytes. Mutagenesis 26:43–49

    Article  CAS  Google Scholar 

  • Heddle JA, Cimino MC, Hayashi M, Romagna F, Shelby MD, Tucker JD, Vanparys Ph, Mac Gregor JT (1991) Micronuclei as an index of cytogenetic damage: past, present, and future. Environ Mol Mutagen 18:277–291

    Article  CAS  Google Scholar 

  • Helleday T (2003) Pathways for mitotic homologous recombination in mammalian cells. Mutat Res 532:103–115

    Article  CAS  Google Scholar 

  • Hilliard CA, Armstrong MJ, Bradt CI, Hill RB, Greenwood SK, Galloway SM (1998) Chromosome aberrations in vitro related to cytotoxicity of nonmutagenic chemicals and metabolic poisons. Environ Mol Mutagen 31:316–326

    Article  CAS  Google Scholar 

  • Horváthová E, Turcaňiová V, Slameňova D (2007) Comparative study of DNA-damaging and DNA-protective effects of selected components of essential plant oils in human leukemic cells K562. Neoplasma 54:478–483

    Google Scholar 

  • Horváthová E, Slameňova D, Maršálková L, Šramková M, Wsólová L (2009) Effects of borneol on the level of DNA damage induced in primary rat hepatocytes and testicular cells by hydrogen peroxide. Food Chem Toxicol 47:1318–1323

    Article  Google Scholar 

  • Ishidate Jr, Sofuni T, YoshikawaA K, Hayashi M, Nohmi T, Sawada M, Matsuoka A (1984) Primary mutagenicity screening of food additives currently used in Japan. Food Chem Toxicol 22:623–636

    Article  CAS  Google Scholar 

  • Kayraldiz A, Kocaman AY, Rencüzoğulları E, İstifli ES, İla HB, Topaktaş M, Dağlıoğlu YK (2010) The genotoxic and antigenotoxic effects of Aloe vera leaf extract in vivo and in vitro. Turk J Biol 34:235–246

    CAS  Google Scholar 

  • Kirsch-Volders M, Sofuni T, Aardema M, Albertini S, Eastmond D, Fenech M, Ishidate M Jr, Kirchner S, Lorge E, Morita T, Norppa H, Surrallés J, Vanhauwaert A, Wakata A (2003) Report from the in vitro micronucleus assay working group. Mutat Res 540:153–163

    CAS  Google Scholar 

  • Kordalı S, Kotan R, Mavi A, Çakır A, Ala A, Yıldırım A (2005) Determination of the chemical composition and antioxidant activity of the essential oil of Artemisia dracunculus and of the antifungal and antibacterial activities of Turkish Artemisia absinthium, Artemisia dracunculus, Artemisia santonicum and Artemisia spicigera essential oils. J Agric Food Chem 53:9452–9458

    Article  Google Scholar 

  • Köse EO, Deniz İG, Sarıkürkçü C, Aktaş Ö, Yavuz M (2010) Chemical composition, antimicrobial and antioxidant activities of the essential oils of Sideritis erythrantha Boiss. and Heldr. (var. erythrantha and var. cedretorum P.H. Davis) endemic in Turkey. Food Chem Toxicol 48:2960–2965

    Article  Google Scholar 

  • Lamberti L, Ponzetto BP, Ardito G (1983) Cell kinetics and sister chromatid exchange frequency in human lymphocytes. Mutat Res 319:193–199

    Article  Google Scholar 

  • Mace MLJ, Daskal Y, Wray W (1978) Scanning electron microscopy of chromosome aberrations. Mutat Res 52:199–206

    Article  Google Scholar 

  • Maron DM, Ames BN (1983) Revised methods for the Salmonella mutagenicity test. Mutat Res 113:173–215

    CAS  Google Scholar 

  • Mosciano G (1997) P&F 22 No. 3, 47

  • Moteki H, Hibasami H, Yamada Y, Katsuzaki H, Imai K, Komiya T (2002) Specific induction of apoptosis by 1, 8 cineole in two human leukemia cell lines, but not in human stomach cancer line. Oncol Rep 9:757–760

    CAS  Google Scholar 

  • Nishida N, Tamotsu S, Nagata M, Saito C, Sakai A (2005) Allelopathic effects of volatile monoterpenoids produced by Salvia leucophylla inhibition of cell proliferation and DNA synthesis in the root apical meristem of Brassica campestris seedlings. J Chem Ecol 31:187–1203

    Article  Google Scholar 

  • Pattnaik S, Subramanyam VR, Bapaji M, Köle CR (1997) Antibacterial and antifungal activity of aromatic constituents of essential oils. Microbios 89:39–46

    CAS  Google Scholar 

  • Paz-y-Miño C, Bustamante G, Sánchez ME, Leone PE (2002) Cytogenetic monitoring in a population occupationally exposed to pesticides in Ecuador. Environ Health Perspect 110:1077–1080

    Article  Google Scholar 

  • Perry PE, Thompson EJ (1984) The methodology of sister chromatid exchanges. In: Kilbey BJ, Legator M, Nichols W, Ramel C (eds) Handbook of mutagenicity test procedures, 2nd edn. Elsevier Science Publishers, Amsterdam, pp 495–529

    Google Scholar 

  • Rencuzogullari E, Ila HB, Kayraldiz A, Diler SB, Yavuz A, Arslan M, Kaya FF, Topaktas M (2006) The mutagenic and antimutagenic effects of Ecballium elaterium fruit juice in human peripheral lymphocytes. Russ J Genet 42:623–627

    Article  Google Scholar 

  • Sangun MK, Aydin E, Timur M, Karadeniz H, Caliskan M, Ozkan A (2007) Comparison of chemical composition of the essential oil of Laurus nobilis L. leaves and fruits from different regions of Hatay, Turkey. J Environ Biol 28:731–733

    CAS  Google Scholar 

  • Speit G, Haupter S (1985) On the mechanism of differential giemsa staining of bromodeoxyuridine-substituted chromosomes. II. differences between the demonstration of sister chromatid differentiation and replication patterns. Hum Genet 70:126–129

    Article  CAS  Google Scholar 

  • Tepe B, Donmez E, Unlu M, Candan F, Daferera D, Vardar-Unlu G, Polissiou M, Sokmen A (2004) Antimicrobial and antioxidative activities of the essential oils and methanol extracts of Salvia cryptantha (Montbret et Aucher ex Benth.) and Salvia multicaulis (Vahl). Food Chem 84:519–525

    Article  CAS  Google Scholar 

  • Tucker JD, Auletta A, Cimino MC, Dearfield KL, Jacobson-Kram D, Tice RR, Carrano AV (1993) Sister-chromatid exchange: second report of the gene-tox program. Mutat Res 297:101–180

    CAS  Google Scholar 

  • VCF (2010) Volatile compounds in food:database/Nijssen, In: Ingen-Visscher LM, Van CA, Donders, JJH (eds)–Version 12.2—Zeist (The Netherlands):TNO quality of life, pp 1963–2010

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Acknowledgements

This investigation was supported by a grant from The Scientific and Technical Research Council of Turkey, Ankara (TUBITAK, Project No. 109T546).

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Correspondence to Ayşe Yavuz Kocaman.

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Kocaman, A.Y., Rencüzoğulları, E., Topaktaş, M. et al. The effects of 4-thujanol on chromosome aberrations, sister chromatid exchanges and micronucleus in human peripheral blood lymphocytes. Cytotechnology 63, 493–502 (2011). https://doi.org/10.1007/s10616-011-9372-7

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  • DOI: https://doi.org/10.1007/s10616-011-9372-7

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