2,2',4,4'-四溴联苯醚和2,2',4,4',5-五氯联苯联合作用的细胞遗传毒性

目的 研究2,2',4,4'-四溴联苯醚(2,2',4,4'-tetrabromodiphenyl ethers,PBDE-47)和2,2',4,4',5-五氯联苯(2,2',4,4',5-hexachlorobiphenyl,PCB153)联合作用的细胞遗传毒性.方法 体外培养的SH-SY5Y细胞暴露于2、4、8mol/LPBDE-47或(和)5mol/LPCB153 24 h后,采用噻唑盐(MTT)、单细胞凝胶电泳、胞质分裂阻滞以及SDS-KCl沉淀法分别检测细胞活力、DNA损伤、微核和DNA-蛋白交联(DPC)形成情况.结果 与单独PBDE-47染毒组比较,各联合染毒组核分裂指数(NDI)明显下降,微核率、微核细胞率和DPC明显增加,Olive尾矩增大,尾部DNA百分率升高,差异均有统计学意义(P＜0.05).≥4 mol/L PBDE-47+5 mol/L PCB153联合染毒细胞存活率明显低于相应剂量的PBDE-47和PCB153单独染毒组,差异有统计学意义(P＜0.05).≥2mol/LPBDE-47+5mol/L PCB153联合染毒组微核率、微核细胞率、DPC均明显高于PCB153单独染毒组;≥4 mol/L PBDE-47+5 mol/L PCB153联合染毒组细胞NDI低于PCB153单独染毒组;Olive尾矩和尾部DNA百分率仅8 μmol/L PBDE-47+5μmol/LPCB153联合染毒组高于PCB153单独染毒组,差异均有统计学意义(P＜0.05).析因分析显示,两者在抑制细胞存活、诱导DNA损伤、微核和DPC形成等方面存在交互作用,差异有统计学意义(P＜0.01),表现为协同作用方式.结论 一定剂量的PBDE-47与PCB153联合可抑制细胞存活,诱导DNA损伤、微核和DPC形成,呈现细胞遗传毒性,两者联合作用类型为协同作用.

Cytogenetoxicity induced by 2,2', 4,4'-tetrabromodiphenyl ethers combined with 2,2',4,4',5-hexachlorobiphenyl treatment in SH-SY5Y cells

OBJECTIVE: To investigate the cytogenetoxicity of 2, 2', 4, 4'-tetrabromodiphenyl ethers (PBDE-47) combined with 2, 2', 4, 4', 5-hexachlorobiphenyl (PCB153) treatment in SH-SY5Y cells. METHODS: Exponentially growing SH-SY5Y cells were exposed to different concentrations of PBDE-47 or/and PCB153 for 24 h in vitro. Cell viability, DNA damage, chromosome abnormalities, and DNA-protein crosslinks (DPC) were measured using MTT, comet assay, cytokinesis-block micronucleus (CBMN) test, and SDS-KCl assay respectively. RESULTS: Compared to the each single PBDE-47 groups, the nuclear division index (NDI) was significantly lower (P < 0.05) and the frequencies of micronuclei (MNI), percentage of DNA in the tail, Olive tail moment and DPC were significantly increased (P < 0.05) in the PBDE-47 combined with PCB153 groups. There was a statistical decrease in cell viability in groups of 4 micromol/L PBDE-47 and above combined with PCB153 than that in contrast to the same dose of PBDE-47 group or PCB153 alone (P < 0.05). Significant increase was found in MNI frequency and DPC in 2 micromol/L PBDE-47 and above combined with PCB153 than those in the single PCB153 group (P < 0.05). In the groups of 4 micromol/L PBDE-47 and above combined with PCB153, the cell NDI were significantly lower than that of the single PCB153 group (P < 0.05). Compared to the single PCB153 group, the percentage of DNA in the tail and Olive tail moment was significantly increased in the 8 micromol/L PBDE-47 combined with 5 micromol/L PCB153. Factorial analysis showed that interactions between PBDE-47 and PCB153 existed in inhibiting cell viability, inducing DNA damage, MNI, and DPC formation (P < 0.01), and possessing synergistic effects. CONCLUSION: Some dose of PBDE-47 combined with PCB153 can inhibit cell viability, induce DNA damage, DPC formation, and chromosome abnormalities. The pattern of the combined effect is synergistic in cytogenotoxicity.