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目的通过给动物模型吸入氨基甲苯评价性别对其代谢的影响及与体内氧化性损伤程度的关系,为探讨不同性别间致癌物质代谢差异对肺癌发生发展过程中的影响提供理论依据。方法采用8周龄雌、雄小鼠(c57BL/6)各16只,按照吸入暴露气体和性别不同分成4组。经暴露7 d后,测定肺、肝组织中的CYP2E1表达量;用高效液相色谱法测定尿中马尿酸和硫代巴比妥酸反应产物(TBARS);用酶脱免疫吸附测定试剂盒(ELISA kit)测定尿中8-羟脱氧鸟苷(8-OHd G)。结果暴露组中肺和肝组织中CYP2E1表达均明显增加。无论暴露组或对照组,雌性小鼠CYP2E1表达量、尿中8-OHd G、TBARS浓度均显著高于雄性小鼠。肝组织中CYP2E1 m RNA表达量与尿中马尿酸、TBRAS、8-OHd G浓度呈正相关关系,差异无统计学意义。结论该研究发现小鼠经氨基甲苯暴露后不同性别间氨基甲苯代谢存在差异并导致不同程度的体内氧化损伤,提示肺癌易感性和性别不同导致的致癌物质代谢差异有关。
OBJECTIVE: To evaluate the effect of sex on the metabolism and the degree of oxidative damage induced by sex in animal models by inhalation of aminotoluene, and to provide a theoretical basis for exploring the influence of carcinogenic metabolism among different genders on the occurrence and development of lung cancer. Methods 16 female and male 8-week-old mice (c57BL / 6) were randomly divided into 4 groups according to the inhalation exposure gas and gender. After exposure for 7 days, the expression of CYP2E1 in lung and liver tissues was determined. The urinary hippuric acid and thiobarbituric acid reaction products (TBARS) were determined by HPLC. The enzyme-linked immunosorbent assay kit ELISA kit) for determination of urinary 8-hydroxydeoxyguanosine (8-OHd G). Results The CYP2E1 expression in the lung and liver tissues of the exposed group was significantly increased. The CYP2E1 expression, urinary 8-OHd G and TBARS concentrations in female mice were significantly higher than those in male mice in both exposure and control groups. The expression of CYP2E1 mRNA in liver tissue was positively correlated with the concentrations of hippuric acid, TBRAS and 8-OHd G in urine. The difference was not statistically significant. Conclusions This study found that the metabolism of aminotoluene between different genders in mice after exposure to aminotoluene is different and leads to different degrees of oxidative damage in vivo, suggesting that carcinogenic metabolism may be related to susceptibility to lung cancer and gender differences.