Abstract
BACKGROUND: To establish a model of pancreatic cancer induced by 7,12-dimethylbenzantracene (DMBA) in Sprague-Dawley (SD) rats, and detect the expression of DNA-repair proteins (MGMT, ERCC₁, hMSH₂, and hMLH₁) and their significance in pancreatic cancer and non-cancerous pancreatic tissues of SD rats. METHODS: DMBA was directly implanted into the parenchyma of rat pancreas (group A and group B), and group B rats were then treated with trichostatin A (TSA). The rats in both groups were executed within 3 to 5 months, and their pancreatic tissues were observed by macrography and under microscopy. Meanwhile, the rats in the control group (group C) were executed at 5 months. Immunohistochemistry was used to assay the expression of MGMT, ERCC₁, hMSH₂, and hMLH₁. RESULTS: The incidence of pancreatic cancer in group A within 3 to 5 months was 48.7% (18/37), including 1 case of fibrosarcoma. The incidence of pancreatic cancer in group B was 33.3% (12/36), including 1 case of fibrosarcoma. The mean of maximal diameters of tumors in group A was higher than that in group B (P <0.05). No pathological changes were found in pancreas of group C and other main organs (except pancreas) of group A and group B. No statistical differences were found among the positive rates of MGMT, ERCC₁, hMSH₂, and hMLH₁ in ductal adenocarcinoma and non-cancerous pancreatic tissues of group A (P >0.05). The positive rates of MGMT, ERCC₁, hMSH₂, and hMLH₁ were significantly lower in ductal adenocarcinoma than those in non-cancerous tissues of group B (P ≤0.05). All pancreas of group C had positive expression of MGMT, ERCC₁, hMSH₂, and hMLH₁ and two cases of fibrosarcoma showed a negative expression. CONCLUSIONS: DMBA, directly implanted into the parenchyma of pancreas, creates an ideal pancreatic cancer model within a short time. TSA might restrain DNA damage related to the genesis and growth of pancreatic cancer in rats. The DNA-repair proteins, including MGMT, ERCC₁, hMSH₂, and hMLH₁, might play an important role in the genesis of pancreatic cancer induced by DMBA in rats.