Effect On Methylation And P53，c-Fos，c-Jun Expression On Mice Hepatic Induced By Beryllium Sulfate

Objective：To observe beryllium sulfate (BeSO4·4H2O) induced hepatotoxicity on mice viaanimal experiment, and explored the effect on methylation and methylation status onpromoter of p53, c-fos, c-jun gene and expression of mice hepatotoxicity induced byberyllium sulfate. To approach the epigenetics mechanism on mice hepatotoxicity thatinduced by beryllium sulfate.Methods：1.36six-weeks-old male Kunming (KM) mice were randomly divided into3groups. One group was designated as normal control was administered with sterilesaline solution by intraperitoneal injection (0.1ml/10g body weight); the rest of twoexperimental groups were administered with1mg/kg and2mg/kg sterile salinesolution of beryllium sulfate respectively by intraperitoneal injection respectively,every other day for four weeks. The general statuses about developmental conditionof mice were observed.2. All mice were sacrificed by neck breaking method.Part of liver were stainedby Hematoxylin-feosin and obversed the change of pathologic histology on lightmicroscope. The rest of liver were isolated and stored at-80℃for DNA extraction.3. Status of DNA methylation were monitored by high performance liquidchromatography（HPLC）;The methylation status on promoter of p53,c-fos,c-jun genewere detected by methylation specific PCR（MSP）; The expression of protein p53,c-Fos, and c-Jun were measured by immunohistochemisty. Results：1. As for the liver histopathology changes under light microscope，hepatic cordswere clearly, hepatic sinusoid were normal and central veins were completely incontrol group；But in beryllium sulfate groups focal necroses were occurred aroundhepatic blood vessels and different extent of karyopyknosis were appeared withinfiltrating of inflammatory cells.2. Compared with the control group, the global levels of DNA methylation in allexperimental groups were significantly higher than controls (P<0.05)；The2mg/kggroup showed obvious higher than the1mg/kg group (P<0.01).3. Methylation of p53,c-fos and c-jun genes promoter CpG islands were notdetected in control group，but methylation of the three genes were detected inexperimental groups.Conclusions：1. Beryllium sulfate can induce obvious hepatotoxicity on mice.2. Beryllium sulfate can increase the global levels of DNA methylation and leadto p53, c-fos, c-jun genes promoter CpG islands methylated.3. The alteration of epigenetics induced by Beryllium sulfate on hepar wasprobably one of the mechanism of its hepatotoxicity.