[Genotoxicity study of Cortex Fraxini decoction].
OBJECTIVE
To investigate the genotoxicity of Cortex Fraxini decoction.


METHODS
Mouse lymphoma assay (MLA) and mouse bone marrow micronucleus test (MNT) were used. In MLA, four dose levels of 1.71, 3.42, 6.83 and 13.65 g (crude drug) x L(-1) were exposed with I5178Y cells for 3 hours with and without metabolic activation, then expressed for 2 days. The mutation frequency plates were prepared and incubated for 12-13 days. Colony size in each plate was scored, and the total mutation frequency and the percentage of small colony mutants were calculated. In MNT, contained three dose levels of 7.14, 14.28 and 28.55 mg (crude drug) x kg(-1) and 10 ICR mice (5 males/5 females) were in each group. The mice were given in every 24 hours by oral gavage twice and sacrificed after 24 hours of the last dosing. Both femur bones were collected to prepare the smear. For each mouse, the number of micronucleated polychromatic erythrocytes (MNPCE) in 2 000 polychromatic erythrocytes was counted, and the mean of rate of MNPCE of each group was calculated.


RESULTS
In MLA, the results indicated that the total mutation frequency of four dose levels showed a dose-dependent increase, there was statistically significant difference at high concentrations compared with negative control (P < 0.01), and the percentage of small colony mutants was similar with positive control in the absence of metabolic activation. The total mutation frequency of each dose level was similar with negative control in the presence of metabolic activation. In MNT, the results indicated that the decoction did not show inhibitory action for bone marrow, and the induced rate of MNPCE of each group was not significantly increased comparing with negative control.


CONCLUSIONS
Cortex Fraxini decoction induces the tk(+/-) gene mutation and chromosome damage in L5178Y cells in vitro without metabolic activation, it hints that the direct mutagens may be within the test article. Cortex Fraxini decoction does not show chromosome damage of bone marrow in ICR mice, it has not genotoxicity in vitro/in vivo with metabolic activation under this study condition.
Hu
Yanping
Y
National Center for Safety Evaluation of Drugs, National Institute for the Control of Pharmaceutical and Biological Products, Beijing, 100176, China. huer64@126.com
Song
Jie
J
Wang
Xin
X
Zhang
Min
M
Wang
Xiuwen
X
Li
Bo
B
D031319:Aesculus; D000818:Animals; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000633:toxicity*; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009152:Mutagenicity Tests; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity*; D009154:Mutation / Q000187:drug effects
D004365:Drugs, Chinese Herbal; D009153:Mutagens; C517354:horse chestnut seed