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首页> 外文期刊>The Journal of toxicological sciences >Relationship between DNA damage and micronucleus in mouse liver
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Relationship between DNA damage and micronucleus in mouse liver

机译：DNA损伤与小鼠肝脏微核的关系

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To determine the optimum timing of partial hepatectomy (PH) in a previously developed mouse liver micronucleus test (Igarashi and Shimada, 1997), the relation between DNA damage and micronucleus was examined using the in vivo alkaline comet assay and the micronucleus test on the liver of the same individual mouse. Five genotoxic carcinogens, 1-nitropyrene (1-NP) (125 mg/kg), cyclophosphamide (CP) (50 mg/kg), methylmethan sulfonate (MMS) (80 mg/kg), mitomycin C (MMC) (2 mg/kg) and diethylnitrosamine (DEN) (50 mg/kg) were intraperitoneally dosed to each group consisting of 4 male ddY mice. The mice were subjected to PH 3, 8 or 24 hr after dosing of each carcinogen, and comet assay was performed using the removed liver. The regenerated hepatocyte was sampled five days after PH, and the incidence of micronucleus was measured. CP, MMS, MMC and DEN induced DNA damage at 8 and 24 hr after dosing, while 1-NP induced DNA damage only 8 hr after dosing. All five carcinogens induced micronuclei whenever PH was performed. In the case of CP, the peak of DNA damage was 24 hr after dosing and the timing of PH did not remarkably affect the incidence of micronuclei. The other 4 carcinogens showed peak DNA damage at 8 hr and the highest incidence of micronuclei when PH was operated 24 hr after dosing. In conclusion, we are the first to show the relation of induction between DNA damage and micronucleus in the liver from the same mouse, and tentatively showed the optimal timing of PH as 24 hr after dosing.
机译：为了在先前开发的小鼠肝脏微核试验（Igarashi和Shimada，1997）中确定部分肝切除术（PH）的最佳时机，使用体内碱性彗星试验和肝脏微核试验检查了DNA损伤与微核之间的关系。相同的单个鼠标。五个遗传毒性致癌物，1-硝基py（1-NP）（125 mg / kg），环磷酰胺（CP）（50 mg / kg），甲磺酸甲酯（MMS）（80 mg / kg），丝裂霉素C（MMC）（2 mg / kg）和二乙基亚硝胺（DEN）（50 mg / kg）腹膜内给药至每只由4只雄性ddY小鼠组成的组。每种致癌物的剂量给药后，小鼠接受PH 3、8或24小时，并使用取出的肝脏进行彗星试验​​。 PH后5天取样再生的肝细胞，并测量微核的发生率。 CP，MMS，MMC和DEN在给药后8和24小时引起DNA损伤，而1-NP仅在给药后8小时引起DNA损伤。每当执行PH时，所有五个致癌物都会诱导微核。在CP的情况下，DNA损伤的高峰是在给药后24小时，而PH的时间并没有显着影响微核的发生。在给药后24小时进行PH操作时，其他4种致癌物在8小时显示出最大的DNA损伤，并且微核的发生率最高。总之，我们是第一个显示同一只小鼠肝脏中DNA损伤与肝脏微核之间的诱导关系的人，并初步显示了给药后24小时的最佳PH时机。

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