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纸质出版日期:2012
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赵源, 吴文斌, 汤家铭. 雄黄致体内外染色体畸变[J]. 中国实验方剂学杂志, 2012,18(14):245-249.
ZHAO Yuan, WU Wen-bin, TANG Jia-ming. Studies on and Hamster Chromosome Aberration Induced by Realgar[J]. Chinese journal of experimental traditional medical formulae, 2012, 18(14): 245-249.
目的: 用仓鼠体内染色体畸变试验和中国仓鼠肺细胞CHL细胞染色体畸变试验评价雄黄的遗传毒性。 方法: 体内染色体畸变试验用毛足属仓鼠连续ig 5 d给予33.25
66.5
133 mg·kg-1剂量雄黄悬浊液
处死前2 h ip 秋水仙素。处死后取骨髓细胞制备染色体。油镜下观察每只动物骨髓细胞的有丝分裂指数和100个中期分裂相细胞的畸变类型。CHL细胞染色体畸变试验用雄黄浸出液终质量浓度为0.15
0.3
0.6 g·L-1 作用于CHL细胞
培养24 h或48 h
终止培养前4 h加入秋水仙素。收获细胞
制备染色体
油镜下观察CHL细胞有丝分裂指数和200个中期分裂相细胞的畸变类型。 结果: ①雄黄265.0 mg·kg-1组和雄黄530.0 mg·kg-1组 ig 给药和雄黄浸出液(1.2
2.4 g·L-1 )作用于CHL细胞显示有明显的抑制有丝分裂作用。②与阴性对照组比较
雄黄 ig 给药仓鼠体内染色体畸变率和雄黄体外给药CHL细胞染色体畸变率均显著升高
差异有极显著意义
且有明显的量效关系。但体内试验的畸变率低于体外试验。③雄黄给药后CHL细胞染色体畸变试验中可见较多的染色体断片
而仓鼠体内染色体畸变试验中未发现
这可能与体内外药物作用的方式不同。 结论: ①雄黄能致体内外细胞染色体畸变
具有遗传毒性。②仓鼠体内染色体畸变试验可作为中药新药遗传毒性评价试验组合的方法之一。
Objective: To evaluate the genetic toxicity of realgar by using Hamster in vivo chromosome aberration test and CHL cells chromosome aberration test. Method: For in vivo chromosome aberration test
hamsters (Phodopus sungorus) were used to realgar suspension at doses of 33.25
66.5
133 mg·kg-1 respectively for 5 days by ig administration. Colchicine was injected intraperitoneally 2 h before sacrificed. Bone marrow cells were taken to prepare chromosome smears. Mitotic index of bone marrow cells and types of chromosome aberration in 100 metaphase cells per animal were observed under the microscope oil lens. For CHL cells chromosome aberration test
realgar extracts were used to cells at final doses of 0.15
0.3
0.6 g·L-1
cultured for 24 h or 48 h. Colchicine was added at 4 h before harvesting and preparing chromosome smears. Mitotic index of CHL cells and types of chromosome aberration in 200 metaphase cells per dose were observed under the microscope oil lens. Result: ① Obvious mitosis inhibition effects were found at doses of 265.0
530.0 mg·kg-1 realgar suspensions in vivo chromosome aberration test
and of 1.2
2.4 g·L-1 final extract concentrations in CHL cell chromosome aberration test. ②Compared with the negative control
the chromosome aberration rates in both in vivo chromosome aberration test and CHL cell chromosome aberration test after administration were statistically significant increased
and had dose-effect relations. The aberration rate was lower in vivo test than in vitro test. ③More chromosome fragments could be found in in vitro test
while no chromosome fragments was found in in vivo test. The difference may be caused by different drug-cell reactions in in vitro and in vivo. Conclusion: ①Realgar can cause chromosome aberrations both in vitro and in vivo
therefore has genotoxicity effect. ②Hamster (P.sungorus) in vivo chromosome aberration test can be used as one of the test battery for evaluating Chinese medicine genotoxicity.
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