丙烯酰胺对F344大鼠肝毒性的分子机制研究

doi:10.3969/j.issn.1004-616x.2016.03.003

癌变·畸变·突变 ›› 2016, Vol. 28 ›› Issue (3): 174-178.doi: 10.3969/j.issn.1004-616x.2016.03.003

丙烯酰胺对F344大鼠肝毒性的分子机制研究

赖怡^1,2, 陈佳红^1,2, 张航^1,2, 乐聪^1,2, 姜岩^1,3, 陈涛^1,2

1. 苏州大学医学部公共卫生学院, 江苏苏州 215123;
2. 江苏省老年病预防与转化医学重点实验室, 江苏苏州 215123;
3. 苏州大学医学部生物科学与基础医学学院, 江苏苏州 215123

收稿日期:2015-11-09 修回日期:2016-02-13 出版日期:2016-05-31 发布日期:2016-05-31
通讯作者: 陈涛,Tel:0512-65882273;E-mail:tchen@suda.edu.cn E-mail:tchen@suda.edu.cn
作者简介:赖怡,E-mail:24959733@qq.com。
基金资助:
教育部留学回国人员科研启动基金;江苏高校优势学科建设工程资助项目;国家自然科学基金(81300143)

Molecular mechanisms of hepatoxicity caused by acrylamide in F344 rats

LAI Yi^1,2, CHEN Jiahong^1,2, ZHANG Hang^1,2, YUE Cong^1,2, JIANG Yan^1,3, CHEN Tao^1,2

1. School of Public Health, Medical College of Soochow University, Suzhou 215123;
2. Key Laboratory of Prevention and Translational Medicine Geriatrics in Jiangsu Province, Suzhou 215123;
3. School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, Jiangsu, China

Received:2015-11-09 Revised:2016-02-13 Online:2016-05-31 Published:2016-05-31

摘要/Abstract

摘要： 目的:通过检测丙烯酰胺对大鼠肝脏基因表达、DNA甲基化以及基因突变的影响,探讨其肝脏毒性的分子机制。方法:以含50 μg/mL丙烯酰胺的饮用水染毒7周龄F344雌性大鼠28 d;采用荧光定量PCR方法检测肝脏细胞增殖以及DNA甲基化调控相关基因的mRNA表达水平;结合重亚硫酸盐的限制性内切酶分析方法检测Cdkn1a/Cdkn2a基因启动子区和重复序列Line-1的DNA甲基化水平;PCR扩增测序方法检测H-ras基因突变。结果:丙烯酰胺引起大鼠肝脏中Dnmt3a、Cdkn1a、Cdkn2a、Jun和Line-1的mRNA水平表达下降;未检测到Cdkn1a/Cdkn2a基因启动子区DNA和重复序列Line-1甲基化的变化;测序结果发现丙烯酰胺未引起H-ras基因突变。结论:丙烯酰胺可引起大鼠肝脏中细胞增殖相关基因表达的变化,但无DNA甲基化改变和基因突变。

关键词: 丙烯酰胺, mRNA, DNA甲基化, 肝毒性, 基因突变

Abstract: OBJECTIVE:This study was aimed to investigate molecular mechanisms of acrylamide (AA)-induced hepatotoxicity by examining the effects on mRNA expression, DNA methylation and gene mutations in F344 female rats. METHODS:F344 female rats aged 7 weeks were orally dosed with 0 and 50 μg/mL of AA in drinking water for 28 d. Using qPCR, we detected mRNA expression level of genes which were involved with cell proliferationand and with regulation of DNA methylation in livers. The promoter DNA methylation status of Cdkn1a, Cdkn2a and repetitive sequence Line-1 were examined by COBRA. We also examined the mutation levels of H-ras gene by PCR sequencing. RESULTS:Compared with control, AA decreased mRNA expression levels of Dnmt3a, Cdkn1a, Cdkn2a, Jun and Line-1 in F344 rat liver. No significant change was found in the global DNA methylation and the promoter methylation status of Cdkn1a and Cdkn2a. Moreover, no gene mutation of H-ras was found. CONCLUSION:AA induced expression changes of genes which were involved in DNA methylation regulation and cell proliferation but no alteration in DNA methylation in rat livers. However, no gene mutation was detected

Key words: acrylamide, mRNA, DNA methylation, hepatotoxicity, gene mutation

中图分类号:

R114

赖怡, 陈佳红, 张航, 乐聪, 姜岩, 陈涛. 丙烯酰胺对F344大鼠肝毒性的分子机制研究[J]. 癌变·畸变·突变, 2016, 28(3): 174-178.

LAI Yi, CHEN Jiahong, ZHANG Hang, YUE Cong, JIANG Yan, CHEN Tao. Molecular mechanisms of hepatoxicity caused by acrylamide in F344 rats[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2016, 28(3): 174-178.

参考文献

[1] Pelucchi C,Galeone C,Levi F,et al. Dietary acrylamide and human cancer[J]. Int J Cancer,2006,118(2):467-471.
[2] Mei N,McDaniel LP,Dobrovolsky VN,et al. The genotoxicity of acrylamide and glycidamide in big blue rats[J]. Toxicol Sci,2010,115(2):412-421.
[3] Ghorbel I,Elwej A,Jamoussi K,et al. Potential protective effects of extra virgin olive oil on the hepatotoxicity induced by co-exposure of adult rats to acrylamide and aluminum[J]. Food Funct,2015,6(4):1126-1135.
[4] Zhang X,Zhao C,Jie B. Various dietary polyunsaturated fatty acids modulate acrylamide-induced preneoplatic urothelial proliferation and apoptosis in mice[J]. Exp Toxicol Pathol,2010,62(1):9-16.
[5] Zenick H,Hope E,Smith MK. Reproductive toxicity associated with acrylamide treatment in male and female rats[J]. J Toxicol Environ Health,1986,17(4):457-472.
[6] Von Tungeln LS,Doerge DR,Gamboa da Costa G,et al. Tumorigenicity of acrylamide and its metabolite glycidamide in the neonatal mouse bioassay[J]. Int J Cancer,2012,131(9):2008-2015.
[7] Beland FA,Mellick PW,Olson GR,et al. Carcinogenicity of acrylamide in B6C3F(1) mice and F344/N rats from a 2-year drinking water exposure[J]. Food Chem Toxicol,2013,51:149-159.
[8] Alhosin M,Sharif T,Mousli M,et al. Down-regulation of UHRF1,associated with re-expression of tumor suppressor genes,is a common feature of natural compounds exhibiting anti-cancer properties[J]. J Exp Clin Cancer Res,2011,30:41.
[9] Szyf M. The implications of DNA methylation for toxicology:toward toxicomethylomics,the toxicology of DNA methylation[J]. Toxicol Sci,2011,120(2):235-255.
[10] Cazzalini O,Scovassi AI,Savio M,et al. Multiple roles of the cell cycle inhibitor p21(CDKN1A) in the DNA damage response[J]. Mutat Res,2010,704(1/2/3):12-20.
[11] Liu J,Benbrahim-Tallaa L,Qian X,et al. Further studies on aberrant gene expression associated with arsenic-induced malignant transformation in rat liver TRL1215 cells[J]. Toxicol Appl Pharmacol,2006,216(3):407-415.
[12] Tao L,Yang S,Xie M,et al. Effect of trichloroethylene and its metabolites,dichloroacetic acid and trichloroacetic acid,on the methylation and expression of c-Jun and c-Myc protooncogenes in mouse liver:prevention by methionine[J]. Toxicol Sci,2000,54(2):399-407.
[13] Rapanelli M,Frick LR,Zanutto BS. Differential gene expression in the rat hippocampus during learning of an operant conditioning task[J]. Neuroscience,2009,163(4):1031-1038.
[14] Counts JL,Sarmiento JI,Harbison ML,et al. Cell proliferation and global methylation status changes in mouse liver after phenobarbital and/or choline-devoid,methionine-deficient diet administration[J]. Carcinogenesis,1996,17(6):1251-1257.
[15] Sohn YW,Lee GH,Liem A,et al. Activation of H-ras oncogenes in male B6C3F1 mouse liver tumors induced by vinthionine or 2-chloroethyl methyl sulfide[J]. Carcinogenesis,1996,17:1361-1364.
[16] Elpek GO,Unal B,Bozova S. H-ras oncogene expression and angiogenesis in experimental liver cirrhosis[J]. Gastroenterol Res Pract,2013. doi:10.1155/2013/868916.
[17] Fox TR,Schumann AM,Watanabe PG,et al. Mutationalanalysis of the H-ras oncogene in spontaneous C57BL/6 x C3H/He mouse liver tumors and tumors induced with genotoxic and nongenotoxic hepatocarcinogens[J]. Cancer Res,1990,50:4014-4019.
[18] Koyama N,Yasui M,Kimura A,et al. Acrylamide genotoxicity in young versus adult gpt delta male rats[J]. Mutagenesis,2011,26(4):545-549.

丙烯酰胺对F344大鼠肝毒性的分子机制研究

Molecular mechanisms of hepatoxicity caused by acrylamide in F344 rats

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