SD大鼠灌胃盐酸丙卡巴肼与乌拉坦的多脏器碱性彗星实验研究
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篇名: SD大鼠灌胃盐酸丙卡巴肼与乌拉坦的多脏器碱性彗星实验研究
TITLE:
摘要: 目的:通过碱性彗星实验评价盐酸丙卡巴肼(PCZ)和乌拉坦(EC)对大鼠不同脏器的DNA损伤效应,验证多脏器碱性彗星实验的可行性。方法:取30只SD大鼠按体质量随机分成6组,每组5只,分别为阴性对照组(超纯水)、PCZ 75 mg/kg组、PCZ 150 mg/kg组、EC 400 mg/kg组、EC 800 mg/kg组以及阳性对照组(N-乙基-N-亚硝基脲,40 mg/kg)。大鼠连续灌胃给药4 d,实验期间观察其临床症状并记录体质量,末次给药后3 h内处死大鼠,称肝、肾、肺质量,收集肝、肾、肺及外周血淋巴细胞,制备成单细胞悬液进行碱性彗星实验。样本分别经裂解、解旋、电泳、染色等步骤后,使用Komet 6.0软件进行图像分析尾DNA含量百分率(尾DNA%)、尾距。结果:与阴性对照组比较,PCZ 75、150 mg/kg组和阳性对照组大鼠给药4 d后体质量和肝、肾质量均明显降低(P<0.05或P<0.01),EC 800 mg/kg组大鼠给药4 d后仅体质量明显降低(P<0.05或P<0.01),其余差异均无统计学意义(P>0.05)。与阴性对照组比较,PCZ 75、150 mg/kg组和阳性对照组大鼠肝、肾、肺和外周血淋巴细胞的尾DNA%和尾距均明显增加(P<0.05或P<0.01),其中PCZ对肝、肺的影响程度更明显;EC 800 mg/kg组大鼠肝、肾和外周血淋巴细胞的尾DNA%和尾距均明显增加(P<0.05或P<0.01),EC 400 mg/kg组大鼠仅肾组织的尾DNA%和尾距明显增加(P<0.05)。结论:PCZ诱导的细胞DNA损伤较强,肝和肺是其遗传毒性作用的易感器官;EC诱导的细胞DNA损伤相对较弱,肾是其遗传毒性作用最敏感的器官。
ABSTRACT: OBJECTIVE: To evaluate the DNA damage response of procarbazine hydrochloride (PCZ) and ethyl carbamate (EC) to different tissues in rats by performing alkaline comet assay, to validate the feasibility of alkaline comet assay of various tissues. METHODS: Totally 30 SD rats were randomly divided into 6 groups according to body weight, with 5 rats in each group, such as negative control group (hyperpure water), PCZ 75 mg/kg group, PCZ 150 mg/kg group, EC 400 mg/kg group, EC 800 mg/kg group, positive control group (N-ethyl-N-nitrosourea 40 mg/kg). Those rats were given relevant medicine intragasttrically for 4 d; clinical symptoms of rats were observed and body weight was recorded during experiment. Within 3 h after last medication, the rats were sacrificed; liver, renal and lung weight were weighed; liver, kidney, lung and peripheral blood lymphocytes were collected. The single cell suspension was prepared to perform alkaline comet assay. After lysis, unwind, electrophoresis and dying, tail DNA% and tail distance of samples were analyzed by Komet 6.0 software. RESULTS: Compared with negative control group, body weight, liver and renal weight of rats were decreased significantly in PCZ 75 mg/kg group, PCZ 150 mg/kg group and positive control group 4 d after medication (P<0.05 or P<0.01). Body weight of rats were decreased significantly in EC 800    mg/kg 4 d after medication (P<0.05 or P<0.01); there was no statistical significance (P>0.05). Compared with negative control group, tail DNA% and tail distance in liver, kidney and peripheral blood lymphocytes were increased significantly in PCZ 75    mg/kg group, PCZ 150 mg/kg group and positive control group (P<0.05 or P<0.01); PCZ showed more significant effects on liver and lung. Tail DNA% and tail distance of liver, kidney and peripheral blood lymphocytes were increased significantly in EC 800 mg/kg group (P<0.05 or P<0.01), and tail DNA% and tail distance of renal tissue was increased significantly in EC 400   mg/kg group (P<0.05). CONCLUSIONS: PCZ induced stronger DNA damage; liver and lung are the major genotoxicity target of PCZ. EC-induced DNA damage is relatively weak, and kidney is the most sensitive organ for EC-induced genotoxicity.
期刊: 2019年第30卷第1期
作者: 文海若,陈高峰,任璐,毛志慧,宋捷,汪祺
AUTHORS: WEN Hairuo,CHEN Gaofeng,REN Lu,MAO Zhihui,SONG Jie,WANG Qi
关键字: 碱性彗星实验;体内遗传毒性;盐酸丙卡巴肼;乌拉坦;SD大鼠
KEYWORDS: Alkaline comet assay; in vivo genotoxicity; Procarbazine hydrochloride; Ethyl carbamate; SD rats
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