Evaluation of the Genotoxicity of Decursin and Decursinol Angelate Produced by Angelica gigas Nakai

In this study, we assessed the stability and toxicological safety of Angelica gigas Nakai (A. gigas Nakai) extract, which is comprised of decursin and decursinol angelate (D/DA). D/DA was tested for mutagenicity using Ames Salmonella tester strains (TA102, TA1535, and TA1537) with or without metabolic activation (S9 mix). No increase in the number of revertants was observed in response to any of the doses tested (1.25, 12.5, 125, and ). In addition, a chromosome aberration test was conducted in the Chinese hamster lung (CHL) cell line. To accomplish this, cells were treated with D/DA (3.28, 13.12, 52.46, and ) or with Mitomycin C () as a positive control in the case of no metabolic activation or benzo(a)pyrene () in the case of metabolic activation. No significant increase in chromosome aberrations was observed in response to treatment with any of these concentrations, regardless of activation of the metabolic system. According to these results, we concluded that D/DA did not induce bacterial reverse mutation or clastogenicity in vitro in the range of concentrations evaluated in these experiments.

[1]  Mi Kyeong Lee,et al.  The simultaneous determination of coumarins in Angelica gigas root by high performance liquid chromatography-diode array detector coupled with electrospray ionization/mass spectrometry. , 2008, Journal of pharmaceutical and biomedical analysis.

[2]  R. Agarwal,et al.  A novel anticancer agent, decursin, induces G1 arrest and apoptosis in human prostate carcinoma cells. , 2005, Cancer research.

[3]  S. Kang,et al.  Anti-tumor activities of decursinol angelate and decursin fromAngelica gigas , 2003, Archives of pharmacal research.

[4]  S. Kang,et al.  Antibacterial coumarins fromAngelica gigas roots , 2003, Archives of pharmacal research.

[5]  S. Sung,et al.  Coumarins isolated from Angelica gigas inhibit acetylcholinesterase: structure-activity relationships. , 2001, Journal of natural products.

[6]  류재천,et al.  DNA Damage와 Apoptosis를 정량화하는 단세포전기영동법 ( Single Cell Gel Electrophoresis ( comet assay ) to Detect DNA Damage and Apoptosis in Cell Level ) , 1997 .

[7]  K. Ahn,et al.  Decursin: a cytotoxic agent and protein kinase C activator from the root of Angelica gigas. , 1996, Planta medica.

[8]  V. Mersch-Sundermann,et al.  Sources of variability of the Escherichia coli PQ37 genotoxicity assay (SOS chromotest). , 1991, Mutation research.

[9]  T. Sofuni,et al.  The micronucleus assay with mouse peripheral blood reticulocytes using acridine orange-coated slides. , 1990, Mutation research.

[10]  J. Jenderny,et al.  Chromosomal abnormalities and sister-chromatid exchange in bone marrow cells of mice and Chinese hamsters after inhalation and intraperitoneal administration: I. Diepoxybutane. , 1987, Mutation research.

[11]  B. Ames,et al.  Revised methods for the Salmonella mutagenicity test. , 1983, Mutation research.

[12]  P. Jeggo,et al.  Chromosomal rearrangement and carcinogenesis. , 1982, Mutation research.

[13]  M. Ishidate,et al.  Chromosome tests with 134 compounds on Chinese hamster cells in vitro--a screening for chemical carcinogens. , 1977, Mutation research.

[14]  B. Ames,et al.  Detection of carcinogens as mutagens in the Salmonella/microsome test: assay of 300 chemicals: discussion. , 1976, Proceedings of the National Academy of Sciences of the United States of America.

[15]  B. Ames,et al.  Carcinogens are mutagens: a simple test system combining liver homogenates for activation and bacteria for detection. , 1973, Proceedings of the National Academy of Sciences of the United States of America.

[16]  M. Konoshima,et al.  Coumarins from the root of Angelica gigas Nakai. , 1968, Chemical & pharmaceutical bulletin.

[17]  C. Dunnett.  A Multiple Comparison Procedure for Comparing Several Treatments with a Control , 1955 .

[18]  J. Kim,et al.  Genetic Toxicity Test of 8-Hydroxyquinoline by Ames, Micronucleus, Comet Assays and Microarray Analysis , 2007 .

[19]  Young-beob Yu.  Evaluation on the Safety of gamma-Irradiated Angelica gigas Nakai: Stability of Active Components and Safety in Genotoxicity Test , 2000 .

[20]  M. Shelby,et al.  Multilaboratory comparison of in vitro tests for chromosome aberrations in CHO and CHL cells tested under the same protocols , 1997, Environmental and molecular mutagenesis.

[21]  H. Nagase,et al.  Evaluation of the SOS chromotest for the detection of antimutagens , 1991, Environmental and molecular mutagenesis.

[22]  Youn-Jung Kim,et al.  Evaluation of the Genetic Toxicity of Systhetic Chemicals(IX) - a Synthetic Selective Herbicide, Pretilachor - , 1986 .

[23]  F. Zimmermann.  Induction of mitotic gene conversion by mutagens. , 1971, Mutation research.