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部分肝切除对大鼠肝脏提取物从烷基化DNA中去除O6-甲基鸟嘌呤的影响。

Effect of partial hepatectomy on removal of O6-methylguanine from alkylated DNA by rat liver extracts.

作者信息

Pegg A E, Perry W, Bennett R A

出版信息

Biochem J. 1981 Jul 1;197(1):195-201. doi: 10.1042/bj1970195.

Abstract
  1. The activity of an enzyme catalysing the loss of O6-methylguanine from methylated DNA was increasing during liver regeneration after partial hepatectomy. Activity was increased 3-fold by 24h and was maximal (6-fold increase) over the period 48-72h after operation. 2. This activity could also be induced by chronic treatment with dimethylnitrosamine, but the maximal response amounted to a 2-3-fold change (with the greater effect in male rats) after 4-6 weeks of exposure to daily doses of 2 mg of dimethylnitrosamine/kg. 3. Neither partial hepatectomy nor treatment with dimethylnitrosamine increased the activities of two other enzymes repairing alkylated DNA, DNA (7-methylguanine-)glycosylase and DNA (3-methyladenine-)glycosylase. 4. These results therefore indicate that there is a selective induction of the O6-methylguanine removal system during hepatocyte proliferation. Since this product is known to lead to mutations and its persistence in DNA throughout cell replication has been implicated in tumour initiation, this induction may play a role in resistance to carcinogenesis by alkylating agents.
摘要
  1. 在部分肝切除术后肝脏再生过程中,催化甲基化DNA上O6-甲基鸟嘌呤去除的酶的活性增强。术后24小时活性增加了3倍,在术后48 - 72小时达到最大值(增加了6倍)。2. 用二甲基亚硝胺长期处理也可诱导这种活性,但在每天给予2毫克/千克二甲基亚硝胺,连续暴露4 - 6周后,最大反应为2 - 3倍变化(雄性大鼠的效应更大)。3. 部分肝切除或用二甲基亚硝胺处理均未增加另外两种修复烷基化DNA的酶,即DNA(7-甲基鸟嘌呤)糖基化酶和DNA(3-甲基腺嘌呤)糖基化酶的活性。4. 因此,这些结果表明在肝细胞增殖过程中存在O6-甲基鸟嘌呤去除系统的选择性诱导。由于已知该产物会导致突变,并且其在整个细胞复制过程中在DNA中的持续存在与肿瘤起始有关,这种诱导可能在对烷基化剂致癌作用的抗性中发挥作用。

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