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目的研究杜仲水煎剂的遗传毒性。方法采用小鼠淋巴瘤细胞试验(MLA)和小鼠骨髓微核试验(MNT)。在MLA中,2.5、5、10、20 mg.ml-1生药4个浓度组在非代谢活化(-S9)和代谢活化(+S9)条件下与L5178Y细胞作用3 h,表达2 d,制备基因突变频率平板并培养12 d,计数大、小突变细胞集落的孔数,计算总突变率(MF)和小集落突变百分率(SC%);在MNT中,12.8、25.6、51.2 g.kg-1生药3个剂量组间隔24 h灌胃给药2次,制作骨髓涂片,计数每只小鼠两千个嗜多染红细胞中含微核的嗜多染红细胞数,计算每组动物嗜多染红细胞的平均微核率。结果4个浓度组在+/-S9条件下诱发的MF呈现剂量相关性增加,与阴性对照组比较有统计学意义(P<0.05),-S9条件下的SC%与阳性对照组相仿,+S9条件下的SC%随浓度增加而升高。各剂量组未显示骨髓抑制作用,诱发的微核率与阴性对照组比较未见明显增加。结论杜仲水煎剂在+/-S9条件下均可诱发L5178Y细胞tk位点突变并导致染色体损伤,提示对人体具有潜在的遗传毒性;但供试品对小鼠骨髓细胞染色体无损伤,经体内代谢活化后未显示遗传毒作用。
Objective To study the genetic toxicity of Eucommia water decoction. Methods Mouse lymphoma cell assay (MLA) and mouse bone marrow micronucleus test (MNT) were used. In MLA, 2.5 concentrations of 2.5, 5, 10, and 20 mg.ml-1 of crude drug were treated with L5178Y cells for 3 hours under conditions of non-metabolic activation (-S9) and metabolic activation (+S9) for 2 days. Gene mutation frequency was plated and cultured for 12 days. The number of large and small mutant cell colonies was counted, and the total mutation rate (MF) and the percentage of small colony mutations (SC%) were calculated; in MNT, 12.8, 25.6, 51.2 g.kg- 1 The three doses of crude drug were intragastrically administered twice at intervals of 24 h to prepare bone marrow smears. The number of micronucleated polychromatic red blood cells in two thousand polychromatic erythrocytes per mouse was counted, and the number of animals per group was calculated. The average micronucleus rate of erythrocytes. Results The MF induced by +/-S9 in the four concentration groups showed a dose-related increase, compared with the negative control group (P<0.05). The SC% under the -S9 condition was similar to that of the positive control group. SC% under S9 conditions increased with increasing concentrations. There was no evidence of myelosuppression in each dose group, and there was no significant increase in the frequency of induced micronucleus compared with the negative control group. Conclusion The decoction of Eucommia ulmoides can induce mutation of tk site of L5178Y cells and cause chromosome damage under +/-S9 conditions, suggesting that it has potential genotoxicity to the human body; but the test product has no damage to the chromosome of mouse bone marrow cells and is transmitted through the body. No genetic toxicity was shown after metabolic activation.