Qin G, Ning Y, Su J, Shinozuka H, Lotlikar P D
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Exp Mol Med. 1998 Dec 31;30(4):186-91. doi: 10.1038/emm.1998.27.
The effect of carbon tetrachloride (CCl4) on aflatoxin B1 (AFB1)-induced enzyme altered hepatic foci has been examined in young male Fischer rats given AIN-76A diet. A single i.p. dose of AFB1 (0.2 mg/kg body wt) was given to rats 24 h after partial hepatectomy. Two weeks later, CCl4 (0.8 ml/kg body wt) was injected i.p. once a week for 9 weeks. Animals were sacrificed 24 h after the last dose of CCl4 and glutathione S-transferase placental form (GST-P) and gamma-glutamyl transpeptidase (GGT) positive hepatic foci were analyzed by immunohistochemical and histochemical methods, respectively. Ten weeks after AFB1 dosing, treatment with CCl4 increased the number of AFB1-induced enzyme altered foci several fold and produced a ten to twenty-fold increase in area and volume. GST-P was more sensitive than GGT in detecting AFB1-induced enzyme altered foci. Treatment with AFB1 or CCl4 produced mild hepatic fibrosis in zones 1 and 3 respectively, whereas both treatments produced severe fibrosis in zones 1 to 3 areas. Treatment with CCl4 after AFB1 dosing lowered hepatic GSH levels by 20% and increased lipid peroxidation by 40%. It appears that CCl4, by being an effective enhancer of AFB1-induced enzyme altered hepatic foci in the rat, may mimic cirrhosis observed in human hepatocellular carcinoma.
在给予AIN - 76A饮食的年轻雄性Fischer大鼠中，研究了四氯化碳（CCl4）对黄曲霉毒素B1（AFB1）诱导的酶改变型肝灶的影响。在部分肝切除术后24小时，给大鼠腹腔注射单次剂量的AFB1（0.2 mg/kg体重）。两周后，每周一次腹腔注射CCl4（0.8 ml/kg体重），共9周。在最后一次注射CCl4后24小时处死动物，分别通过免疫组织化学和组织化学方法分析谷胱甘肽S - 转移酶胎盘型（GST - P）和γ-谷氨酰转肽酶（GGT）阳性肝灶。AFB1给药10周后，用CCl4处理使AFB1诱导的酶改变型病灶数量增加了几倍，面积和体积增加了10至20倍。在检测AFB1诱导的酶改变型病灶方面，GST - P比GGT更敏感。用AFB1或CCl4处理分别在1区和3区产生轻度肝纤维化，而两种处理在1至3区均产生严重纤维化。AFB1给药后用CCl4处理使肝脏谷胱甘肽水平降低20%，脂质过氧化增加40%。看来，CCl4作为大鼠中AFB1诱导的酶改变型肝灶的有效增强剂，可能模拟人类肝细胞癌中观察到的肝硬化。
