Genotoxicity Study of CJ-11555

CJ-11555의 유전독성에 관한 연구

  • Published : 2004.06.01

Abstract

To evaluate the genotoxicity of CJ-11555, an anti-cirrhotic agent, the reverse mutation test, chromosomal aberration test and in vivo micronucleus test in rats were performed. In the reverse mutation test, the treatment of CJ-11555 at doses of 33.3, 100, 333, 1000, 3330 and 5000 $\mu\textrm{g}$/plate with and without 89 did not induce mutagenicity in Salmonella typhimurium TA98, TA100, TA1535, TA1537, and Escherichia coli (E. call) WP2uvrA. In chromosomal aberration test, CJ-11555 did not induce structural a chromosomal aberration in Chinese hamster ovary (CHO) cells with and without metabolic activation at all doses. In micronucleus test, CJ-11555 did not induce any statistically significant increases in micronucleated polychromatic erythrocyte (MNPCE) at doses of 500, 1000, and 2000 mg/kg. These results suggest that CJ-11555 might not have a mutagenic potential under the conditions in this study.

Keywords

References

  1. Ames, B.N., McCann, J. and Yamasaki, E. (1975): Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test. Mutation Research, 31, 347-364 https://doi.org/10.1016/0165-1161(75)90046-1
  2. Ansher, S. (1985): The chemotherapy of schistosomiasis. Ann. Rev. Pharmacol., 25, 485-508
  3. Beers, M.H. and Berkow, R. (1999): The Merck manual of diagnosis and therapy, 17th edition. (Accessed on-line).
  4. Green, M.H.L. and Muriel, W.J. (1976): Mutagen testing using trp reversion in Escherichia coli. Mutation Research, 38, 3-32 https://doi.org/10.1016/0165-1161(76)90076-5
  5. Kang, K.W., Kim, Y., Cho, M.K., Bae, S.K., Kim, C.W., Lee, M.G. and Kim, S.G. (2002): Oltipraz regenerates cirrhotic liver through CCAAT/enhancer binding protein-mediated stellate cell inactivation. The FASEB Journal, 16, 1988-1990
  6. Klensler, T.W. and Helzlsouer, K.J. (1995): Oltipraz : clinical opportunities for cancer chemoprevention. J. Cell Biochem Suppl. P. 22, 101-107
  7. Kensler, T.W., Egner, P.A., Wang, J.B., Zhu, Y.R., Zhang, B.C., Qian, G.S., Kuang, S.Y., Gange, S.J., Jacobson, L.P., Munoz, A. and Groopman, J.D. (2002): Stratergies for chemoprevention of liver cancer. Eur. J. Cancer Prev. 2, 58-64
  8. OECA (1977): OECD guideline for the testing of chemicals, Documents 471, Genetic Toxicology: Bacterial Reverse Mutation Test, Organization for Economic Cooperation and Development, Paris, France
  9. OECA (1977): OECD guideline for the testing of chemicals, Documents 47e, Genetic Toxicology: In vitro Mammalian Chromosomal Aberration Test, Organization for Economic Cooperation and Development, Paris, France
  10. OECA (1977): OECD guideline for the testing of chemicals, Documents 47e, Genetic Toxicology: Mammalian Erythrocyte Micronucleus Test, Organization for Economic Cooperation and Development, Paris, France
  11. Thakur, A.J., Berry, K.J. and Mielke, P.W., Jr. (1985): A FORTRAN program for testing trend and homogeneity in proportions. Computer Programs in Biomedicine, 19, 229-233 https://doi.org/10.1016/0010-468X(85)90015-7
  12. Wattenberg, L.W. (1985): Chemoprevention of cancer. Cancer Res., 45, 1-8
  13. Watternberg, L.W. and Bueding, E. (1986): Inhibitory effects of 5-(2-pyrazinyl)-4-methyl-1,2-dithiol-3-thione (Oltipraz) on carcinogenesis induced by benzo[a]pyren, diethylnitrosamine and uracil mustard. Carchinogenesis, 7, 1379-1381. https://doi.org/10.1093/carcin/7.8.1379