The Role And Potential Mechanism Of PARG Deficiency In The Carcinogenesis Of Benzopyrene

ObjectiveLung cancer,as one of the most common malignant tumors in the world,is a serious threat to human life and health,the prevention and treatment of lung cancer still remains a major medical problem.PARG play an important role in the occurrence of tumors.In this study,PARG-deficient mice were treated with long-term BaP through respiratory to investigate the role and possible mechanisms of PARG in BaP-induced lung cancer,and the pathogenesis of lung cancer was clarified to provide reference for the effective prevention and treatment of lung cancer.Method6-8 weeks old,wild mouse and PARG^+/-mice each 24.Grouped by type and gender,divides it randomly into the control group and the esposed group.Using the dynamic inhalation poison cabinet for 90 days and 180 days,the BaP of the esposed group was 10ug/m3and the control group was 0 ug/m3.The survival status and body mass of mice were recorded.At the end of the study,the mice lungs and blood were collected.Pathological analysis of lungs was performed by HE staining,the BaP exposure in the blood of mice was detected by ELISA,and the expression of EGFR and UCH-L1 in mouse lungs was detected by RT-PCR and Western blot technique.Immunohistochemical method was used to verify the expression of EGFR and UCH-L1 in lung tissue.Results1.BaP exposure inhibited the weight gain of wild mice,there was no significant effect on PARG^+/-mice:The weight of wild mice was significantly lower than that in the control group?p<0.05?after 90 days and 180 days,while the weight of PARG^+/-mice had no significant difference with the control group after90 days and 180 days of BaP exposure.The weight gain of wild mice after BaP infection was slower than that in PARG^+/-mice,and the difference was statistically significant?p<0.05?.The lung organ coefficients of the wild mice showed a tendency to gain weight,as the BaP exposure time lengthened,while the PARG^+/-mice did not change significantly:the lung organ coefficients of the wild mice after 90 days of BaP were not significantly different from those in the control group,and the lung organ coefficients were significantly heavier than those in the control group?p<0.05?after 180 days.There was no significant change of the lung organ coefficient in PARG^+/-mice after 90 days and 180days.The lung injury in the wild mice increased with the increase of the time of virus exposure,there were severe alveolar diffuse interstitial interstitial in the lungs of the wild miceexposed 180 days by BaP,the alveolar structure was badly damaged,abnormal nodules appeared,pathological analysis was the tumor,and the PARG^+/-mice were exposed with 180 days later,some alveolar interstitial thickening,the alveolar structure was still visible,no abnormal cells were found.The BPDE-DNA concentrations of wild mice and PARG^+/-mice were all higher than those in the control group?p<0.05?,and there was no significant difference between the wild mice and the PARG^+/-mice.2.The relative expression of EGFR,UCH-L1 increased?p<0.05?both gene and proteinin in wild mice after BaP exposure 90 days and 180 days.The expression of PARG^+/-mice's EGFR and UCH-L1 gene was not significantly different after BaP exposed 90 days,but the level of protein expression was decreased?p<0.05?.The expression of EGFR,UCH-L1gene and protein was obviously weakened?p<0.05?in PARG^+/-mice after 180 days exposure.Conclusion1.PARG defeciency inhibited lung cancer BaP-inducedin mice.2.PARG defeciency may inhibit the occurrence of tumors by modulating EGFR signaling and ubiquitin processes.