摘要
目的探讨甲基叔丁基醚(MTBE)对动物致癌的机制。方法小鼠经呼吸道染毒MTBE20d后,取肝、肾、肺细胞进行单细胞凝胶电泳(SCGE)、DNA交联试验及肺和肾组织中丙二醛(MDA)含量测定。对体外培养的大鼠肺Ⅱ型细胞、肝细胞进行SCGE、DNA交联试验和程序外DNA合成试验(UDS)。结果MTBE1440、4968mg/m3组染毒小鼠肝细胞、各剂量组肾细胞、4968mg/m3组肺细胞DNA迁移距离均大于阴性对照组;肝细胞DNA迁移距离与MTBE浓度有剂量-反应关系(r=0.997,P=0.003)。MTBE1440、4968mg/m3组雌性小鼠及4968mg/m3组雄性小鼠肾MDA含量高于阴性对照组,差异有统计学意义(P<0.05)。MTBE浓度>0.050mmol/L时,大鼠肺Ⅱ型细胞、肝细胞DNA迁移距离较阴性对照组增加,差异有统计学意义(P<0.05),且DNA迁移距离与MTBE浓度有剂量-反应关系(r肺=0.967,r肝=0.963,均P<0.05);5.0、10.0mmol/LMTBE组大鼠肺Ⅱ型细胞、肝细胞的3HTrR掺入量每分钟脉冲数(CPM)均高于阴性对照组,差异有统计学意义(P<0.05);各剂量组小鼠肝细胞、大鼠肺Ⅱ型细胞和肝细胞的DNA交联率与阴性对照组的差异均无统计学意义(P>0.05)。结论MTBE对DNA有损伤作用,细胞DNA断裂和脂质过氧化是其引起动物肝、肾肿瘤的可能机制之一。
Objective To investigate the mechanism of-methyl tertiary-butyl ether（MTBE）-induced animal carcinoma. Methods Single cell gel electrophoresis assay（SCGE）, DNA cross-links test and unscheduled DNA synthesis（UDS） assay were conducted with cultured rat type Ⅱ pneumocytes and rat hepatocytes in vitro. Except UDS assay, the same experiment was performed in hepatocytes, renal cells and pneumocytes of mice administrated MTBE by inhalation at 0,108,1 440 and 4 968 mg/m^3 for 20 consecutive days. Simultaneously ,the contents of malondialdehyde（MDA） in homogenates of lung and kidney were determined. Results The lengths of DNA migration in mice hepatocytes at 1440,4 968 mg/m^3 of MTBE,renal cells at all doses of MTBE,and pneumocytes at 4 968 mg/m^3 were greater than those in negtive controls.There was dose-effect relationship between the concentration of MTBE and hepatocytes DNA migration lengths in mice（ r = 0.997, P = 0.003） .MTBE of I 440 and 4 968 mg/m^3 contributed to a rise in MDA of renal homogenates in female mice（ P 〈 0.05）. MTBE above 0.050 mmol/L caused greater DNA migration in cultured rat type 11 pneumocytes and rat hepatocytes in vitro（ P 〈 0.05） ,and also with dose-effect relationship（ rlang = 0. 967, rliver = 0. 963, P 〈 0.05） ）. In UDS assay, DNA synthesis of rat type 11 pneumocytes and rat hepatocytes were increased at the concentration of 5.0 mmol/L and 10.0 mmol/L of MTBE. Conclusion MTBE has some genotoxicity on DNA, and the single strand breaks of cell and lipid peroxication may be one of the possible mechanism of MTBE-induced hepatic and renal tumors of animal.
出处
《中华劳动卫生职业病杂志》
CAS
CSCD
北大核心
2005年第5期362-365,共4页
Chinese Journal of Industrial Hygiene and Occupational Diseases
基金
铁道部科技基金课题(J98Z019)
东南大学医学基金课题(XY0026020)
