Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지

Genotoxicity Study of AS6, a Triterpenoid Derivatives

  • Kwon, Jung (R＆D Center of Dong Kook Pharmaceutical Co., LTD.,) ;
  • Lee, Michael (R＆D Center of Dong Kook Pharmaceutical Co., LTD.) ;
  • Cha, Kyung-Hoi (R＆D Center of Dong Kook Pharmaceutical Co., LTD.) ;
  • Kim, Jong-Choon (Department of Pharmacology and Toxicology, College of Veterinary Medicine Chonnam National University) ;
  • Han, Jung-Hee (Korea Institute of Toxicology, KRICT)
  • Published : 2003.09.01
Download PDF
⟨ Previous Next ⟩

Abstract

To assess the genotoxicity of AS6, several classical toxicological tests were performed. In Ames test, AS6 did not show any transformation of revertant with or without S-9 metabolic activating system, indicating the lack of mutagenic effect of the compound. To assess clastogenic effect, in vivo micronucleus and in vitro chromosomal aberration assays were performed using male ICR mice and Chinese hamster lung (CHL) fibroblast cells, respectively. Chromosomal aberration was not induced regardless of the presence of S-9 metabolic activating system. In addition, AS6 did not cause any increase in the incidence of micronucleated polychromatic erythrocytes at any of the dose levels, suggesting little clastogenicity in vitro or in vivo. Taken together, these results demonstrate that AS-6 has no mutagenic effect in our test system.

Keywords

References

  1. Galloway, S. M. (2000). Cytotoxicity and chromosome aberrations in vitro: Experience in industry and the case for an upper limit on toxicity in the aberration assay. Environ. Mol. Mutagen. 35, 191-201 https://doi.org/10.1002/(SICI)1098-2280(2000)35:3<191::AID-EM6>3.0.CO;2-4
  2. Han, 1, Lee, M., Im, D., Cha, K, Kim, J. C. and Chung, M.K (2003). Toxicity study of AS6, a triterpenoid derivatives: 4 weeks repeated oral administration in rats. J. Applied Phann. 11,72-79
  3. Hayashi, M., MacGregor, 1. T. and Gatehouse, D. G. (2000). In vivo rodent erythrocyte micronucleus assay. II. Some aspects of protocol design including repeated treatments, integration with toxicity testing and automated scoring. Environ. Mol. Mutagen. 35, 234-252 https://doi.org/10.1002/(SICI)1098-2280(2000)35:3<234::AID-EM10>3.0.CO;2-L
  4. Henderson, L., Cole, R., Cole J., Cole H., Aghamohammdi Z. and Regan T. (1984). Sister-chromatid exchange and micronucleus induction as indicators of genetic damage in maternal and fetal cells. Mutat. Res. 126, 47-52 https://doi.org/10.1016/0027-5107(84)90168-4
  5. Koyama, H., Utakoji, T. and Ono, T. (1970). A new cell line derived from newborn Chinese hamster lung tissue. Gann 61, 161-167
  6. Krishna, G. and Hayashi, M. (2000). In vivo rodent micronucleus assay: protocol, conduct and data interpretation. Mutat. Res. 455, 155-166 https://doi.org/10.1016/S0027-5107(00)00117-2
  7. Maron, D. M. and Ames, B. N. (1983). Revised methods for the Salmonella mutagenicity test. Mutat. Res. 113, 173-215 https://doi.org/10.1016/0165-1161(83)90010-9
  8. Maquart, F. X., Chastang, E, Simeon, A., Birembaut, P., Gillery, P. and Wegrowski, Y. (1999). Triterpenes from Centella asiatica stimulate extracellular matrix accumulation in rat experimental wounds. Eur. J. Dennatol. 9, 289-296
  9. Muller, L. and Sofuni, T. (2000). Appropriate levels of cytotoxicity for genotoxicity tests using mammalian cells in vitro. Environ. Mol. Mutagen. 35, 202-205 https://doi.org/10.1002/(SICI)1098-2280(2000)35:3<202::AID-EM7>3.0.CO;2-Q
  10. Nishino, H., Nishino, A., Takayasu, J., Hasegawa, T., Iwashima, A., Hirabayashi, K, Iwata, S. and Shibata, S. (1988). Inhibition of the tumor promoting action of 12-0-tetradecanoylpbobol- 13-acetate by some oleanane-type triterpenoid compounds. Cancer Res. 48, 5210-5215
  11. NRC (National Research Council) (1996). Guide for the Care and Use of Laboratory Animals. National Academy, Washington
  12. Preston, R. J., Dean, B. J., Galloway, S., Holden, H., McFee, A. E and Shelby, M. (1987). Mammalian in vivo cytogenetic assays. Analysis of chromosome aberrations in bone marrow cells. Mutat. Res. 189, 157-165 https://doi.org/10.1016/0165-1218(87)90021-8
  13. Price, K R., Johnson, 1.T. and Fenwick, G. R. (1987). The chemistry and biological significance of saponins in foods and feeding stuffs. CRC Crit. Rev. Food Sci. Nutr. 26,27-135 https://doi.org/10.1080/10408398709527461
  14. Salamone, M. F. and Heddle, J. A. (1983). The bone marrow micronucleus assay: rationale for a revised protocol, in: de Serres FJ (Ed.), Chemical Mutagens: principles and methods for their detection, Vol. 8, Plenum Press, New York, pp. 111149
  15. Schmid, W. (1975). The micronucleus test. Mutat. Res. 31, 1-9 https://doi.org/10.1016/0165-1161(75)90055-2
  16. Tan, P. v., Njimi, C. K and Ayafor, 1. F. (1997). Screening of some african medicinal plants for antiulcerogenic activity: Part 1. Phytotherapy Research 11, 45-47 https://doi.org/10.1002/(SICI)1099-1573(199702)11:1<45::AID-PTR945>3.0.CO;2-I
  17. Tice, R. R., Boucer, R., Luke, C. A. and Shelby, M.D. (1987) Comparative cytogenetic analysis of bone marrow damage induced in B6C3F mice by multiple exposures to gaseous 1,3bytadine. Environ. Mutagen. 9, 235-250 https://doi.org/10.1002/em.2860090303
  18. Tinwell, H. and Ashby, J. (1989). Comparison of acridine orange and Giernsa stains in several mouse bone marrow micronucleus assay - including a triple dose study. Mutagenesis 4, 476-481 https://doi.org/10.1093/mutage/4.6.476