Molecular & Cellular Toxicology

The Korean Society of Toxicogenomics and Toxicoproteomics (대한독성유전 단백체학회)
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Genotoxicity Assessment of Gardenia Yellow using Short-term Assays

  • Chung, Young-Shin (Medvill Co., Ltd.) ;
  • Eum, Ki-Hwan (Department of Biology, College of Natural Sciences, University of Incheon) ;
  • Ahn, Jun-Ho (Department of Biology, College of Natural Sciences, University of Incheon) ;
  • Choi, Seon-A (Medvill Co., Ltd.) ;
  • Noh, Hong-June (Medvill Co., Ltd.) ;
  • Seo, Young-R. (Department of Pharmacology, Institute for Basic of Medical Science, School of Medicine, Kyung Hee University) ;
  • Oh, Se-Wook (Korea Food Research Institute) ;
  • Lee, Michael (Department of Biology, College of Natural Sciences, University of Incheon)
  • Published : 2009.09.30
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Abstract

Gardenia yellow, extracted from gardenia fruit, has been widely used as a coloring agent for foods, and thus, safety of its usage is of prime importance. In the current study, short-term genotoxicity assays were conducted to evaluate the potential genotoxic effects of gardenia yellow. The gardenia yellow used was found to contain 0.057 mg/g of genipin, a known biologically active compound of the gardenia fruit extract. Ames test did not reveal any positive results. No clastogenicity was detected by a chromosomal aberration test, even on evaluation at the highest feasible concentration of gardenia yellow. Gardenia yellow was also shown to be non-genotoxic using an in vitro comet assay and a micronucleus test with L5178Y cells, although a marginal increase in DNA damage and micronuclei frequency was reported in the respective assays. Additionally, in vivo micronucleus test results clearly demonstrated that oral administration of gardenia yellow did not induce micronuclei formation in the bone marrow cells of male ICR mice. Taken together, our results indicate that gardenia yellow is not mutagenic to bacterial cells, and that it does not cause chromosomal damage in mammalian cells, either in vitro or in vivo.

Keywords

References

  1. Yamano, T. et al. Hepatotoxicity of gardenia yellow color in rats. Toxicol Lett 44:177-182 (1988) https://doi.org/10.1016/0378-4274(88)90144-0
  2. Sato, S. et al. A 13-week oral dose subchronic toxicity study of gardenia yellow containing geniposide in rats. Food Chem Toxicol 45:1537-1544 (2007) https://doi.org/10.1016/j.fct.2007.02.015
  3. Ozaki, A. et al. Genotoxicity of gardenia yellow and its components. Food Chem Toxicol 40:1603-1610 (2002) https://doi.org/10.1016/S0278-6915(02)00118-7
  4. Inouye, H., Saito, S., Taguchi, H. & Endo, T. Zwei neue iridoidglucoside aus gardenia jasminoides: gardenosid und geniposid. Tetrahedron Lett 10:2347-2350 (1969) https://doi.org/10.1016/S0040-4039(01)88161-2
  5. Endo, T. & Taguchi, H. A new iridoid glycoside from Gardenia jasminoides genipin-1-$\beta$-gentiobioside. Chem Pharm Bull 18:1066-1067 (1970) https://doi.org/10.1248/cpb.18.1066
  6. Takeda, S., Yusada, K., Endo, T. & Aburada, M. Pharmacological studies on iridoid II. Relationship between structures and choleretic actions of iridoid compound. J Pharm Dyn 3:485-492 (1980) https://doi.org/10.1248/bpb1978.3.485
  7. Yamano, T. et al. Hepatotoxicity of geniposide in rats. Food Chem Toxicol 28:515-519 (1990) https://doi.org/10.1016/0278-6915(90)90122-4
  8. Djerassi, C., Gray, J. D. & Kincl, F. A. Naturally occurring oxygen heterocyclics. IX. Isolation and characterization of genipin. J Org Chem 25:2174-2177 (1960) https://doi.org/10.1021/jo01082a022
  9. Akao, T., Kobayashi, K. & Aburada, M. Enzymatic studies on the animal and intestinal bacterial metabolism of geniposide. Biol Pharm Bull 17:1573-1576 (1994) https://doi.org/10.1248/bpb.17.1573
  10. Yamauchi, K., Fujimoto, N., Kuwanoa, S., Inouye, H. & Inoue, K. The mechanism of purgative action of geniposide, and iridodi glucoside of the fruit of gardenia, in mice. Planta Medica 30:39-47 (1976) https://doi.org/10.1055/s-0028-1097691
  11. Choi, H.-Y., Kim, Y.-J., Jeon, H.-K. & Ryu, J.-C. Study on genotoxicity of Crocin, a component of gardenia fruit, in bacterial and mammalian cell systems. Mol Cell Toxicol 4:285-292 (2008)
  12. Ueno, K., Takeda, Y., Iwasaki, Y. & Yoshizaki, F. Simultaneous estimation of geniposide and genipin in mouse plasma using high-performance liquid chromatography. Anal Sci 17:1237-1239 (2001) https://doi.org/10.2116/analsci.17.1237
  13. Lorge, E. et al. SFTG international collaborative study on in vitro micronucleus test I. General conditions and overall conclusions of the study. Mutat Res 607:13-36 (2006) https://doi.org/10.1016/j.mrgentox.2006.04.006
  14. Fenech, M. & Morley, A. A. Measurement of micronuclei in lymphocytes. Mutat Res 147:29-36 (1985) https://doi.org/10.1016/0165-1161(85)90015-9
  15. Hachiya, N. et al. A review of acute toxicity and genotoxicity data on natural food additives (in Japanese). Toxicology Forum 8:91-105 (1985)
  16. Kirsch-Volders, M. et al. Report from the in vitro micronucleus assay working group. Mutat Res 540:153-163 (2003) https://doi.org/10.1016/j.mrgentox.2003.07.005
  17. Oliver, J. et al. SFTG international collaborative study on in vitro micronucleus test V. Using L5178Y cells. Mutat Res 607:125-152 (2006) https://doi.org/10.1016/j.mrgentox.2006.04.004
  18. Rojas, E., Lopez, M. C. & Valverde, M. Single cell gel electrophoresis assay: methodology and applications. J Chromatogr B Biomed Sci Appl 722:225-254 (1999) https://doi.org/10.1016/S0378-4347(98)00313-2
  19. Tice, R. R. et al. Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing. Environ Mol Mutagen 35:206-221 (2000) https://doi.org/10.1002/(SICI)1098-2280(2000)35:3<206::AID-EM8>3.0.CO;2-J
  20. Henderson, L. et al. Sister-chromatid exchange and micronucleus induction as indicators of genetic damage in maternal and foetal cells. Mutat Res 126:47-52 (1984) https://doi.org/10.1016/0027-5107(84)90168-4
  21. Krishna, G. & Hayashi, M. In vivo rodent micronucleus assay: protocol, conduct and data interpretation. Mutat Res 455:155-166 (2000) https://doi.org/10.1016/S0027-5107(00)00117-2
  22. Salamone, M. F. & Heddle, J. A. The bone marrow micronucleus assay: rationale for a revised protocol, de Serres F. J. (Ed.), Chemical Mutagens: principles and methods for their detection, Vol. 8, Plenum Press, New York, 111-149 (1983)
  23. Maron, D. M. & Ames, B. N. Revised methods for the Salmonella mutagenicity test. Mutat Res 113:173-215 (1983) https://doi.org/10.1016/0165-1161(83)90010-9
  24. Dean, B. J. & Danford, N. Assays for the detection of chemically-induced chromosome damage in cultured mammalian cells. Mutagenicity testing-a practical approach (S. Venitt and J. M. Parry, Ed.), 187-232. IRL Press Limited, Oxford, UK (1984)
  25. Fenech, M. The in vitro micronucleus technique. Mutat Res 455:81-95 (2000) https://doi.org/10.1016/S0027-5107(00)00065-8
  26. Kim, J.-Y., Koh, W. S. & Lee, M. Validation of photocomet assay as a model for the prediction of photocarcinogenicity. Toxicol Res 22:423-429 (2006)
  27. Schmid, W. The micronucleus test. Mutat Res 31:1-9 (1975) https://doi.org/10.1016/0165-1161(75)90055-2
  28. Richardson, C. et al. Analysis of data from in vitro cytogenetics assays, Statistical evaluation of mutagenicity test data (Kirkland, D. J. edit.), Cambridge University Press, Cambridge, U.K., 141-154 (1989)