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

Abstract

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

CLC Number:

R114

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.

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Molecular mechanisms of hepatoxicity caused by acrylamide in F344 rats

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