Chromosomal Aberration Assay of Taxol and 10-deacetyI baccatin III in Chinese Hamster Lung Cells In Vilro

  • Ryu, Jae-Chun (Toxicology Laboratory, Doping Control Center) ;
  • Kim, Kyung-Ran (Toxicology Laboratory, Doping Control Center) ;
  • Ryu, Eun-Kyung (Toxicology Laboratory, Doping Control Center) ;
  • Kim, Hyun-Joo (Toxicology Laboratory, Doping Control Center) ;
  • Kwon, Oh-Seung (Toxicology Laboratory, Doping Control Center) ;
  • Song, Choong-Eui (Division of Applied Chemistry, Korea Institute of Science and Technology) ;
  • Mar, Woong-Chon (Natural Products Research Institute, Seoul National University) ;
  • Chang, Il-Moo (Natural Products Research Institute, Seoul National University)
  • Published : 1996.03.01

Abstract

To investigate the clastogenicity of taxol and its precursor, 10-aleacetyl baccatin III, we performed chromosomal aberration assay with chinese hamster lung cells in vitro. The IC$_{50}$ values of taxol and 10-deacetyl baccatin III were determined as $1/16 \times 10^{-4}$ M (5.34 $\mu$g/ml) and $1 \times 10^{-2}$ M (560 $\mu$g/ml) in MTT assay, respectively. It means that the cytotoxicity of taxol revealed 100 times more cytotoxic than 10-deacetyl baccatin III in chinese hamster lung cell line. Nevertheless the strong positive genetic toxicity of taxol in the bone marrow micronucleus assay in vivo which was recently reported, we observed weak positive clastogenicity of taxoi only in the absence of metabolic activation system in the concentration ranges used in this experiment. Moreover, to clarify the involvement of metabolic fate of taxol because of its strong positive result in vivo, 10-deacetyl baccatin III which is a precursor in taxol synthesis, also subjected in chromosomal aberration assay in vitro. However, we observed no clastogenicity of 10-deacetyl baccatin III in this experiment. From above results, it was suggested that the esterification at C-13 appears to be relative for its genetic toxicity in chromosome aberration using chinese hamster lung cell in vitro.

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