Lobe-specific increases in malondialdehyde DNA adduct formation in the livers of mice following infection with Helicobacter hepaticus.
Lobe-specific increases in malondialdehyde DNA adduct formation in the livers of mice following infection with Helicobacter hepaticus.
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感染肝螺杆菌后，小鼠肝脏中丙二醛 DNA 加合物形成的叶特异性增加。
DOI：
10.1093/carcin/22.8.1281
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发表时间：
2001
期刊：
影响因子：
4.7
通讯作者：
Shuker,DE
中科院分区：
文献类型：
--
作者：
Singh,R;Leuratti,C;Josyula,S;Sipowicz,MA;Diwan,BA;Kasprzak,KS;Schut,HA;Marnett,LJ;Anderson,LM;Shuker,DE
肝幽门螺杆菌感染与小鼠慢性肝炎和肝脏肿瘤的发展有关。这种肝癌发生的潜在机制尚不清楚，但氧化应激与h。肝脏感染可导致脂质过氧化和丙二醛的产生。丙二醛可以与DNA中的脱氧鸟苷反应，形成环嘧啶嘌呤-1，n2 -丙二醛-脱氧鸟苷（M1dG）加合物。这种加合物有可能引起突变，最终导致肝癌。本研究的目的是利用免疫槽印迹法确定小鼠肝脏DNA中M1dG的控制水平和感染相关水平。对照组A/J小鼠肝脏中M1dG水平在3、6、9和12个月时平均为每108个核苷酸37.5、36.6、24.8和30.1个加合物。在h的肝脏DNA中检测到较高水平的M1dG。肝炎感染A/JCr小鼠，在3、6、9和12个月时，每108个核苷酸平均含量分别为40.7、47.0、42.5和52.5个加合物。与对照组相比，a /JCr小鼠尾状叶和正中叶的M1dG水平有明显的年龄依赖性增加。在感染小鼠和对照小鼠中，M1dG加合物的叶特异性分布被注意到，与右叶和中叶相比，左叶在所有时间点显示最低的加合物水平。在另一组实验感染h。治疗后12周，肝脏中位8-羟基脱氧鸟苷水平明显高于左叶。总之，这些结果表明M1dG是与h相关的氧化应激的结果。肝脏感染小鼠，并可能在该模型中促进肝癌的发生。
Helicobacter hepaticusinfection is associated with chronic hepatitis and the development of liver tumours in mice. The underlying mechanism of this liver carcinogenesis is not clear but the oxidative stress associated withH.hepaticusinfection may result in induction of lipid peroxidation and the generation of malondialdehyde. Malondialdehyde can react with deoxyguanosine in DNA resulting in the formation of the cyclic pyrimidopurinoneN-1,N2malondialdehyde–deoxyguanosine (M1dG) adduct. This adduct has the potential to cause mutations that may ultimately lead to liver carcinogenesis. The objective of this study was to determine the control and infection-related levels of M1dG in the liver DNA of mice over time, using an immunoslot-blot procedure. The level of M1dG in control A/J mouse livers at 3, 6, 9 and 12 months averaged 37.5, 36.6, 24.8 and 30.1 adducts per 108nucleotides, respectively. Higher levels of M1dG were detected in the liver DNA ofH.hepaticusinfected A/JCr mice, with levels averaging 40.7, 47.0, 42.5 and 52.5 adducts per 108nucleotides at 3, 6, 9 and 12 months, respectively. There was a significant age dependent increase in the level of M1dG in the caudate and median lobes of the A/JCr mice relative to control mice. A lobe specific distribution of the M1dG adduct in both infected and control mice was noted, with the left lobe showing the lowest level of the adduct compared with the right and median lobes at all time points. In a separate series of mice experimentally infected withH.hepaticus, levels of 8-hydroxy-deoxyguanosine were significantly greater in the median compared with the left lobe at 12 weeks after treatment. In conclusion, these results suggest that M1dG occurs as a result of oxidative stress associated withH.hepaticusinfection of mice, and may contribute to liver carcinogenesis in this model.
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影响因子：
1.7
作者：
H. Seto;T. Seto;T. Takesue;T. Ikemura
通讯作者：
T. Ikemura
丙二醛在哺乳动物细胞中的致突变性和细胞毒性
影响因子：
5.3
作者：
T. Yau
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肝癌发生中异质叶反应的生化和形态学研究。
影响因子：
4.7
作者：
Richardson,FC;Boucheron,JA;Dyroff,MC;Popp,JA;Swenberg,JA
通讯作者：
Swenberg,JA
A/JCr 小鼠肝螺杆菌诱导的肝脏肿瘤中缺乏 p53 和 ras 突变。
影响因子：
4.7
作者：
M. Sipowicz;C. Weghorst;Y. Shiao;G. Buzard;R. Calvert;M. Anver;L. Anderson;J. Rice
通讯作者：
J. Rice
肝螺杆菌引起的肝脏肿瘤：机制的考虑。
影响因子：
2.3
作者：
Canella Ka;B. Diwan;Gorelick Pl;Peter J. Donovan;M. Sipowicz;Kazimierz S. Kasprzak;Weghorst Cm;E. Snyderwine;C. Davis;Larry K. Keefer;Kyrtopoulos Sa;S. S. Hecht;M. Wang;Lucy M. Anderson;Jerry M. Rice
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Jerry M. Rice