Assessment of the effect of betaine on p16 and c-myc DNA methylation and mRNA expression in a chemical induced rat liver cancer model.
Assessment of the effect of betaine on p16 and c-myc DNA methylation and mRNA expression in a chemical induced rat liver cancer model.
复制标题
评估甜菜碱对化学诱导的大鼠肝癌模型中 p16 和 c-myc DNA 甲基化和 mRNA 表达的影响
DOI：
10.1186/1471-2407-9-261
复制
发表时间：
2009-07-30
期刊：
影响因子：
3.8
通讯作者：
Zhu HL
中科院分区：
文献类型：
--
作者：
Du YP;Peng JS;Sun A;Tang ZH;Ling WH;Zhu HL
背景
肝癌的发生和发展可能涉及DNA甲基化的异常变化，这导致某些原癌基因（如c-myc）的激活以及某些肿瘤抑制因子（如p16）的失活。甜菜碱作为一种活跃的甲基供体，维持正常的DNA甲基化模式。然而，关于甜菜碱在肝癌发生中的保护作用的研究很少。
方法
4组大鼠分别给予二乙基亚硝胺（DEN）和添加0、10、20和40 g/kg甜菜碱的AIN-93 G饲料（模型组、1%、2%和4%甜菜碱组），对照组不给予DEN，饲喂AIN-93 G饲料。8周和15周后，采用实时定量PCR（Q-PCR）检测p16和c-myc mRNA的表达。采用甲基化特异性PCR分析p16和c-myc启动子内的DNA甲基化状态。
结果
与模型组相比，甜菜碱组大鼠肝脏胎盘型谷胱甘肽S-转移酶（GST-p）阳性灶的数量和面积减少（P0.05）。虽然四个DEN喂养组肝脏中p16启动子甲基化的频率似乎增加，但在8周或15周后这些组之间没有差异（P 0.05）。补充甜菜碱可剂量依赖性地减弱DEN诱导的p16蛋白表达下调和c-myc蛋白表达上调（P0.01）。模型组、2%甜菜碱组和4%甜菜碱组丙二醛（MDA）和谷胱甘肽S-转移酶（GST）含量均明显升高（P0.05）。最后，在2%和4%甜菜碱组中观察到增强的抗氧化能力（T-AOC）。
结论
我们的数据表明，甜菜碱减弱DEN诱导的大鼠肝脏损伤和逆转DEN诱导的mRNA水平的变化。
Background
The development and progression of liver cancer may involve abnormal changes in DNA methylation, which lead to the activation of certain proto-oncogenes, such as c-myc, as well as the inactivation of certain tumor suppressors, such as p16. Betaine, as an active methyl-donor, maintains normal DNA methylation patterns. However, there are few investigations on the protective effect of betaine in hepatocarcinogenesis.
Methods
Four groups of rats were given diethylinitrosamine (DEN) and fed with AIN-93G diets supplemented with 0, 10, 20 or 40 g betaine/kg (model, 1%, 2%, and 4% betaine, respectively), while the control group, received no DEN, fed with AIN-93G diet. Eight or 15 weeks later, the expression of p16 and c-myc mRNA was examined by Real-time PCR (Q-PCR). The DNA methylation status within the p16 and c-myc promoter was analyzed using methylation-specific PCR.
Results
Compared with the model group, numbers and areas of glutathione S-transferase placental form (GST-p)-positive foci were decreased in the livers of the rats treated with betaine (P 0.05). Although the frequency of p16 promoter methylation in livers of the four DEN-fed groups appeared to increase, there is no difference among these groups after 8 or 15 weeks (P 0.05). Betaine supplementation attenuated the down-regulation of p16 and inhibited the up-regulation of c-myc induced by DEN in a dose-dependent manner (P 0.01). Meanwhile, increases in levels of malondialdehyde (MDA) and glutathione S-transferase (GST) in model, 2% and 4% betaine groups were observed (P 0.05). Finally, enhanced antioxidative capacity (T-AOC) was observed in both the 2% and 4% betaine groups.
Conclusion
Our data suggest that betaine attenuates DEN-induced damage in rat liver and reverses DEN-induced changes in mRNA levels.
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DOI：
10.1152/ajpgi.2000.279.6.g1162
发表时间：
2000-12-01
影响因子：
4.5
作者：
Ogborn, MR;Nitschmann, E;Peeling, J
通讯作者：
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DOI：
10.1016/s1383-5718(02)00288-7
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2003-02-05
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影响因子：
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作者：
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影响因子：
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Kharbanda, KK;Rogers, DD;Tuma, DJ
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