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Promotive action of 2-acetylaminofluorene on hepatic precancerous lesions initiated by diethylnitrosamine in rats:Molecular study

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World Journal of Hepatology 2021年第3期13卷 328-342页

作者： Amany Helmy Hasanin Eman K Habib Nesreen El Gayar Marwa Matboli Clinical Pharmacology Department Faculty of MedicineAin Shams UniversityCairo 11318Egypt Anatomy and Embryology Department Faculty of MedicineAin Shams UniversityCairo 11318Egypt Medical Biochemistry and Molecular Biology Department Faculty of MedicineAin Shams UniversityCairo 11381Egypt

BACKGROUND Diethylnitrosamine(DEN)induces hepatic neoplastic lesions over a prolonged *** To investigate the promotive action of 2-acetylaminofluorene(2-AAF)when combined with DEN in order to develop a rat model for induction of precancerous lesion and investigate the molecular mechanism underlying the activity of *** The pre-precancerous lesions were initiated by intraperitoneal injection of DEN for three weeks consecutively,followed by one intraperitoneal injection of 2-AAF at three different doses(100,200 and 300 mg/kg).Rats were separated into naïve,DEN,DEN+100 mg 2-AAF,DEN+200 mg 2-AAF,and DEN+300 mg 2-AAF *** were sacrificed after 10 wk and 16 *** functions,level of alpha-fetoprotein,glutathione S-transferase-P and proliferating cell nuclear antigen staining of liver tissues were *** mRNA level of RAB11A,BAX,p53,and Cyclin E and epigenetic regulation by long-noncoding RNA(lncRNA)RP11-513I15.6,miR-1262(microRNA),and miR-1298 were assessed in the sera and liver tissues of the *** 2-AAF administration significantly increased the percent area of the precancerous foci and cell proliferation along with a significant decrease in RAB11A,BAX,and p53 mRNA,and the increase in Cyclin E mRNA was associated with a marked decrease in lncRNA RP11-513I15.6 expression with a significant increase in both miR-1262 and *** 2-AFF promoted hepatic precancerous lesions initiated through DEN by decreasing autophagy,apoptosis,and tumor suppression genes,along with increased cell proliferation,in a time-and dose-dependent *** actions were mediated under the epigenetic regulation of lncRNA RP11-513I15.6/miR-1262/miR-1298.

关键词： Acetylaminofluorene hepatic precancerous lesion Diethylnitrosamine Autophagy Apoptosis MicroRNA

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