1.Mechanism of radiosensitization effect of berberine on human nasopharyngeal carcinoma in hypoxia
Chi ZHANG ; Qu ZHANG ; Xi YANG ; Baixia YANG ; Qin QIN ; Hongcheng ZHU ; Jia LIU ; Xinchen SUN
Chinese Journal of Radiological Medicine and Protection 2014;(9):663-667
Objective To investigate the radiosensitiation effect of berberine on human nasopharyngeal carcinoma ( NPC) in hypoxia condition and explore the underlying mechanisms. Methods MTT assay, clonogenic assay and flow cytometry were performed to analyze cell proliferation, colony formation and apoptosis, respectively. Male nude mice inoculated subcutaneously with CNE-2 cells were used to examine the radiosensitization effect of berberine in vivo. The expressions of HIF-1α and VEGF were assessed by Western blot. Results Berberine efficiently inhibited the proliferation of CNE-2 cells in time-dependent and dose-dependent fashions with an IC50 of ( 14?9 ± 2?2 ) μmol/L. Clonogenic survival assay showed that berberine ( 5 μmol/L ) sensitized CNE-2 cells to ionizing radiation in hypoxia and its SERD0 was 1?27. Under hypoxic condition, berberine alone (5, 15 μmol/L) could induce apoptosis (t=5?01, 9?02,P<0?05) and it further promoted 8 Gy radiation-induced apoptosis (t =5?31, 9?91,P <0?05). Moreover, berberine significantly delayed the tumor growth in the combination group (berberine +irradiation) compared with the mice received irradiation alone or PBS (t =2?96, 14?52, P <0?05). Immunobloting assay showed that berberine inhibited the upregulation of HIF-1α and VEGF induced by hypoxia in CNE-2 cells. Conclusion Berberine confers radiosensitivity on hypoxic NPC in vitro and in vivo, which is probably associated with the downregulation of HIF-1α and VEGF expressions.
2.Association between XRCC1 polymorphisms and chromosome damage in workers exposed to benzene in jewelcrafting industry
Lijing HUANG ; Zhimin PENG ; Xizhong ZHANG ; Qiangbing YIN ; Hongcheng CHI
Chinese Journal of Industrial Hygiene and Occupational Diseases 2016;34(6):416-420
Objective To investigate the association between the gene polymorphisms of the DNA damage repair gene X-ray repair cross-complementing gene 1 (XRCC1) and susceptibility to chromosome damage in workers exposed to low-concentration benzene in the jewelcrafting industry.Methods A total of 286 workers exposed to benzene in jewelcrafting enterprises were enrolled as study subjects from January 2013 to December 2014.Gas chromatography was used to measure benzene concentration in workplace,cytokinesisblock micronucleus test was used to analyze the level of chromosome damage in peripheral blood,and the Sequenom technique was used to determine the single nucleotide polymorphisms of XRCC1.Results The timeweighted average concentration of benzene in workplace was <0.6 ~1.8 mg/m3,lower than the national occupational exposure limit (6 mg/m3).The distribution of allele frequencies met the Hardy-Weinberg equilibrium in genetics(P>0.05).Increase in age(RR=1.38,95%CI 1.06~3.75) and increase in working years (RR=1.45,95%CI 1.18~2.58) were risk factors for the increase in micronucleus frequency.Compared with those with the wild-type homozygous genotype,the individuals with XRCC1 rs25487 CT genotype showed a significantly higher risk of increase in micronucleus frequency (RR=1.51,95%CI 1.28~3.87,P<0.05),and the individuals with XRCC1 rs1799782 AA genotype also showed a significantly higher risk of increase in micronucleus frequency (RR =1.65,95% CI 1.30~3.12,P<0.05).There was no clear association between XRCC1 rs25489 polymorphisms and micronucleus frequency (P>0.05).Conclusion Exposure to lowconcentration benzene may cause chromosome damage in workers exposed to benzene,and the XRCC1 polymorphisms rs 25487 and rs 1799782 may be associated with chromosome damage induced by benzene.
3.Association between XRCC1 polymorphisms and chromosome damage in workers exposed to benzene in jewelcrafting industry
Lijing HUANG ; Zhimin PENG ; Xizhong ZHANG ; Qiangbing YIN ; Hongcheng CHI
Chinese Journal of Industrial Hygiene and Occupational Diseases 2016;34(6):416-420
Objective To investigate the association between the gene polymorphisms of the DNA damage repair gene X-ray repair cross-complementing gene 1 (XRCC1) and susceptibility to chromosome damage in workers exposed to low-concentration benzene in the jewelcrafting industry.Methods A total of 286 workers exposed to benzene in jewelcrafting enterprises were enrolled as study subjects from January 2013 to December 2014.Gas chromatography was used to measure benzene concentration in workplace,cytokinesisblock micronucleus test was used to analyze the level of chromosome damage in peripheral blood,and the Sequenom technique was used to determine the single nucleotide polymorphisms of XRCC1.Results The timeweighted average concentration of benzene in workplace was <0.6 ~1.8 mg/m3,lower than the national occupational exposure limit (6 mg/m3).The distribution of allele frequencies met the Hardy-Weinberg equilibrium in genetics(P>0.05).Increase in age(RR=1.38,95%CI 1.06~3.75) and increase in working years (RR=1.45,95%CI 1.18~2.58) were risk factors for the increase in micronucleus frequency.Compared with those with the wild-type homozygous genotype,the individuals with XRCC1 rs25487 CT genotype showed a significantly higher risk of increase in micronucleus frequency (RR=1.51,95%CI 1.28~3.87,P<0.05),and the individuals with XRCC1 rs1799782 AA genotype also showed a significantly higher risk of increase in micronucleus frequency (RR =1.65,95% CI 1.30~3.12,P<0.05).There was no clear association between XRCC1 rs25489 polymorphisms and micronucleus frequency (P>0.05).Conclusion Exposure to lowconcentration benzene may cause chromosome damage in workers exposed to benzene,and the XRCC1 polymorphisms rs 25487 and rs 1799782 may be associated with chromosome damage induced by benzene.