非坏死剂量二乙基亚硝胺诱发大鼠肝癌模型的研究

Studies on Liver Cancer Induced by Non-necrotizing Dose of Diethylnitrosamine in Rats

目的 为化学物致癌危险性评价提供合适的肝癌动物模型 ,并寻找其早期敏感指标。方法 应用本室早年已建立的以非坏死剂量的二乙基亚硝为启动剂 ,以苯巴比妥为促进剂诱发大鼠肝癌两阶段模型 ,进一步用 HE染色、胚胎型谷胱甘肽转移酶 (P- GST)和增殖细胞核抗原 (PCNA)免疫组化染色为指标 ,在 3、6、12和 2 4个月末进行观察。结果 经启动剂与促进剂作用的实验组 ,可产生以嗜酸性细胞为主的癌前病变和肿瘤 ;以 P- GST为标识可显示许多单个肝细胞、转变灶及瘤性结节均呈阳性 ;以 HE染色所识别的转变灶及瘤性结节 PCNA表达较高 ,细胞核 /浆比例减小。而且瘤性结节表达较转变灶更显著。结论 肝细胞

Objective To provide an appropriate animal model of liver cancer and sensitive indicator for carcinogen risk assessment. Methods The developmental processes of liver cancers in rats initiated by non necrotizing dose of diethylnitrosamine and promoted by phenobarbital were studied. Results Most of the preneoplastic lesions and liver cancers were made up of eosinophilic cells. The placental glutathione S transferase(P GST) staining could allow a lot of positive single cells, foci and nodules to be seen. But the lesions showed by HE staining expressed higher proliferating cell nuclear antigen(PCNA) than those showed by P GST staining expressed, indicating a greater possibility for these lesions to persist and develop further. The cellular morphologic analysis demonstrated that the ratio of nuclear radii to cytoplasm radii decreased in the cell in PCNA positive expressing nodules. In addition, the nodules showed by P GST expressed higher PCNA than those the foci expressed, indicating an increased possibility to develop further in the nodules. Conclusion PCNA expression may be used as a relatively ideal marker for predicting the potential development of precancerous lesions in the experimental model of rat liver cancer induction.