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目的探讨联苯双酯(DDB)对肝癌发生的化学预防作用。方法采用抗微核实验和抗DNA损伤实验观察DDB的抗突变作用;采用巴豆油诱发的小鼠耳肿胀实验初步探讨DDB的抗促癌活性;建立二乙基亚硝胺(DEN)/苯巴比妥(PB)联合诱发的小鼠肝癌模型,观察小鼠肝脏的病理改变以及DDB对肝癌发生率的影响。结果小鼠提前灌服DDB50、100、200mg/kg,由环磷酰胺(CTX)引起的骨髓嗜多染红细胞(PCE)微核数分别为39.1±6.6、26.9±6.2、20.8±5.9个,与单用CTX(微核数为49.3±8.1个)相比明显降低(P<0.05或P<0.001);在佛波酯(TPA)作用的同时分别加入1、2、4μmol/LDDB,DNA-EB结合物的荧光强度较单加TPA时显著升高(P<0.05或P<0.001);50、100、200mg/kgDDB均能明显抑制致炎剂巴豆油引起的小鼠耳部急性炎性反应,抑制率分别为15.9%、31.4%、32.0%;应用DDB能改善肝脏的病理状态;100和200mg/kgDDB预防给药均能降低肝肿瘤的发生率,其中200mg/kgDDB对肝细胞性肝癌和肝细胞瘤的抑制率分别为57.1%和22.8%。结论 DDB对化学毒物诱发的肝癌发生有一定抑制活性,同时具有降低肝癌发生率的潜能。
Objective To explore the chemopreventive effect of biphenyldiester (DDB) on liver cancer. Methods Anti-micronucleus test and anti-DNA damage experiment were used to observe the anti-mutagenicity of DDB. The anti-promoting activity of DDB was preliminary investigated using the mouse ear swelling test induced by croton oil; diethyl nitrosamine (DEN)/phenylba was established. The mice model of liver cancer induced by BOTO (PB) was combined to observe the pathological changes of liver and the effect of DDB on the incidence of liver cancer. Results The mice were pretreated with DDB 50, 100, 200 mg/kg, and the number of micronuclei of bone marrow polychromatic erythrocytes (PCE) caused by cyclophosphamide (CTX) was 39.1±6.6, 26.9±6.2, 20.8±5.9, respectively. CTX alone (49.3±8.1 micronuclei) was significantly lower (P<0.05 or P<0.001); 1,2,4 μmol/LDDB, DNA-EB was added simultaneously with phorbol ester (TPA). The fluorescence intensity of the conjugate was significantly higher than that of TPA alone (P<0.05 or P<0.001); 50, 100, and 200 mg/kg DDB all significantly inhibited the acute inflammatory response of the ear caused by the inflammatory agent croton oil. The inhibition rates were 15.9%, 31.4%, and 32.0%, respectively; application of DDB improved the pathological state of the liver; 100 and 200 mg/kg DDB prophylaxis reduced the incidence of liver tumors, of which 200 mg/kg DDB was associated with hepatocellular carcinoma and liver. The inhibition rates of cell tumors were 57.1% and 22.8%, respectively. Conclusion DDB has a certain inhibitory activity against the development of hepatocellular carcinoma induced by chemical poisons, and it also has the potential to reduce the incidence of hepatocellular carcinoma.