Genetic Toxicity Test of Glycidol by Ames, Micronucleus, Comet Assays and Microarray Analysis

  • Kim, Ji-H. (College of Pharmacy, Ewha Womans University) ;
  • Kim, Ki-Y. (College of Pharmacy, Ewha Womans University) ;
  • Kwon, Kyoung-J. (College of Pharmacy, Ewha Womans University) ;
  • Go, Seo-Y. (College of Pharmacy, Ewha Womans University) ;
  • Min, Kyung-N. (College of Pharmacy, Ewha Womans University) ;
  • Lee, Woo-S. (Department of Toxicological Researches, National Institute of Toxicological Research, Korea Food and Drug Administration) ;
  • Park, Sue-N. (Department of Toxicological Researches, National Institute of Toxicological Research, Korea Food and Drug Administration) ;
  • Sheen, Yhun-Y. (College of Pharmacy, Ewha Womans University)
  • Published : 2006.12.30

Abstract

The primary use for glycidol is as a stabilizer in the manufacture of vinylpolymers, however, it is also used as an intermediate in the production of pharmaceuticals, as an additives for oil and synthetic hydraulic fluids, and as a diluting agent is same epoxy resins. In this study, we have carried out in vitro genetic toxicity test of glycidol and microarray analysis of differentially expressed genes in response to glycidol. The result of Ames test showed mutations with glycidol treatment in base substitution strain TA1535 both with and without exogenous metabolic activation. Likewise, glycidol showed mutations in frame shift TA98 both with and without exogenous metabolic activation. The result of COMET assay in L5178Y cells with glycidol treatment showed DNA damage both with and without exogenous metabolic activation. Glycidol increased micronuclei in CHO cells both with and without exogenous metabolic activation. 150 Genes were selected as differentially expressed genes in response to glycidol by microarray analysis and these genes would be candidate biomarkers of genetic toxic action of glycidol.

Keywords

References

  1. Affyrnetrix, Inc. (2000). 'GeneChip$\circledR$ Expression Analysis Technical Manual' http://www.affymetrix.com/support/technical/manual/expression_manual.affx
  2. Fenech, M. (2000). The in vitro micronucleus technique. Mutat. Res. 455, 81-95 https://doi.org/10.1016/S0027-5107(00)00065-8
  3. Gatehouse, D., Haworth, S., Cebula, T., Gocke, E., Kier, L., Matsushima, T., Melcion, C., Nohmi, T., Venitt, S. and Zeiger, E. (1994). Recommendations for the performance of bacterial mutation assays. Mutat. Res. 312, 217-233 https://doi.org/10.1016/0165-1161(94)90037-X
  4. Heslot, H. (1962). A quantitative study of biochemical reversions induced in the yeast Schizosaccharomyces pombe by radiations and radiomimetic substances. Abh. Dtsch. Akad. Wiss. Berlin Kl. Med. 1, 193-228
  5. Irwin, R.D., Eustic, S.L., Stefanski, S. and Haseman, J.K. (1996). Carcinogenicity of glycidol in F344 rats and B6C3Fl mice. J. Appl. Toxcol. 16, 201-209 https://doi.org/10.1002/(SICI)1099-1263(199605)16:3<201::AID-JAT333>3.0.CO;2-0
  6. Izard, G. (1973). Mutagenic effects of acrolein and its two epoxides, glydicol and glycidal in Saccharomyces cerevisiae. C.R. Acad. Sci. 276, 3037-3040
  7. Jackson, H., Campbell, I.S.C. and Jones, A.R. (1970). Is glycidol an active intermediate in the antifertility action of alpha-chlorhydrin in male rats? Natrue. 226, 86-87 https://doi.org/10.1038/226086a0
  8. Kaplan, D.L.; Cornell, J.H. and Kaplan, A.M. (1982). Biodegradation of glycidol and glycidyl nitrate. Appl. Environ. Microbiol. 43, 144-150
  9. Kasamatsu, T., Ogura, R., Ikeda, N., Morita, O., Saigo, K., Watabe, H., Saito, Y. and Suzuki, H. (2005). Genotoxicity studies on dietary diacylglycerol (DAG) oil. Food Chern Toxicol. 43(2), 253-260 https://doi.org/10.1016/j.fct.2004.10.001
  10. Kirsch- Voiders, M., Sofuni, T., Aardema, M., Albertini, S., Eastmond, D., Fenech, M., Ishidate, M., Kirchner, S., Lorge, E., Morita, T., Norppa, H., Surralles, J., Vanhauwaert, A. and Wakata, A. (2003). Report from the in vitro micronucleus assay working group. Mutat. Res. 540, 153-163 https://doi.org/10.1016/j.mrgentox.2003.07.005
  11. Kolmark, G. and Giles, N.H. (1955). Comparative studies of monoepoxides as inducers of reverse mutations in Neurospora. Genetics. 40, 890-902
  12. Lijinsky, W., Singer, G.M. and Kovatch, R.M. (1985). Similar carcinogenic effects in rats of l-ethyl-l-nitroso-3-hydroxyethy-lurea and l-hydroxyethyl-l-nitroso-3-ethylurea. Carcinogenesis. 6, 641-643 https://doi.org/10.1093/carcin/6.4.641
  13. Mamber, S.W., Bryson, V. and Katz, S.E. (1984). Evaluation of the Escherichia coli K12 inductest for detection of potential chemical carcinogens. Mutat. Res. 130, 141-151 https://doi.org/10.1016/0165-1161(84)90116-X
  14. Marks, T.A., Gerling, F.S. and Staples, R.E. (1982). Teratogenic evaluation of epichlorohydrin in the mouse and rat and glycidol in the mouse. J. Toxicol. Environ. Health. 9, 87-96 https://doi.org/10.1080/15287398209530144
  15. McCann J., Choi, E., Yamasaki, E. and Ames, B.N. (1975). Detection of carcinogens as mutagens in the Salmonella/microsome test: Assay of 300 chemicals. Proc. Natl. Acad. Sci. USA. 72, 5135-5139
  16. Migliore, L., Rossi, A.M. and Loprieno, N. (1982). Mutagenic action of structurally related alkene oxides on Schizosaccharomyces pombe: The influence, 'in vitro', of mouse-liver metabolizing system. Mutat. Res. 102, 425-37 https://doi.org/10.1016/0165-1218(82)90105-7
  17. National Toxicology Program (NTP) (1986). Toxicology and carcinogenesis studies of diglycidyl resorcinol ether (technical grade) in F334/N rats and B6C3F1 mice. NT? technical report No. 257. pp.222. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health., Bethesda. USA
  18. National Toxicology Program (NTP) (1987). Toxicology and carcinogenesis studies of 1,2-epoxybutane in F334/N rats and B6C3Fl mice. NT? technical report No. 329. pp.176. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, Research Triangle Park., NC. USA
  19. National Toxicology Program (NTP) (1987). Toxicology and carcinogenesis studies of ethylene oxide in B6C3Fl mice. NTP technical report No. 326. pp.114. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, Research Triangle Park., NC. USA
  20. Norppa, H., Hemminki, K., Sorsa, M. and Vainio H. (1981). Effect of monosubstituted epoxides on chromosome aberrations and SCE in cultured human lymphocytes. Mutat Res. 91, 243-250 https://doi.org/10.1016/0165-7992(81)90040-3
  21. Simmon, V.F., Rosenkranz, H.S., Zeiger, E. and Poirier, L.A. (1979). Mutagenic activity of chemical carcinogens and related compounds in the intraperitoneal host-mediated assay. J. Natl. Cancer. Inst. 62, 911-918
  22. Singh, N.T., McCoy, M.T., Tice, R.R. and Schneider, E.L.(1988). A simple technique for quantification of low levels of DNA damage in individual cells. Exp. Cell. Res. 175, 184-191 https://doi.org/10.1016/0014-4827(88)90265-0
  23. Slott, V.L. and Hales, B.F. (1985). Teratogenicity and ernbryolethality of acrolein and structurally related compounds in rats. Teratology. 32, 65-72 https://doi.org/10.1002/tera.1420320110
  24. Thompson, E.D., Coppinger, W.J., Piper, C.E., McCarroll, N., Oberly, T.J. and Robinson, D. (1981). Mutagenicity of alkyl glycidyl ethers in three short-term assays. Mutat. Res. 90, 213-231 https://doi.org/10.1016/0165-1218(81)90002-1
  25. Thompson, E.D. and Gibson, D.P. (1984). A method for determining the maximum tolerated dose for acute in vivo cytogenetic studies. Food Chem. Toxicol. 22, 665-676 https://doi.org/10.1016/0278-6915(84)90277-1
  26. Van Duuren, B.L., Langseth, L., Goldschmidt, B.M. and Orris, L. (1967). Carcinogenicity of epoxides, lactones, and peroxy compounds VI Structure and carcinogenic activity. J. Natl. Cancer. Inst. 39, 1217-1228
  27. Wade, M.J., Moyer, J.W. and Hine, C.H. (1979). Mutagenic action of a series of epoxide. Mutat. Res. 66, 367-371 https://doi.org/10.1016/0165-1218(79)90047-8