Making a model of digestive tract infection and carcinogenisis of Epstein-Barr virus produced by epithelial cell line (GTC) derived from human gastric adenocarcinoma.

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Epstein-Barr virus (EBV) has been implicated in the pathogenesis of some type of gastric adenocarcinoma. We established an epithelial cell line (GTC-4) derived form human gastric cancer tissue. The cell line have a capacity of producing EBV. We further cloned EBV producing cell line GTC-5 from GTC-4 cells and found that digestive tract of Balb/c mice can be infected by EBV produced by GTC-5 (GTC-5-EBV) and finally infected mice developed adenocarcinoma of the digestive tract.Balb/c mice were gavaged with 0.2ml of 50% ethanol to produce gastric mucosal injury and than GTC-5-EBV were gavaged. Histoimmunostaining showed that EBV nuclear antigen NA-2 were positive in the gastric mucosa 24 hours after the gavage of EBV and disappeared in 21 days. NA-1 and LMP-1 (latent membrane protein 1) were also present in gastric mucosa 5 days after the gavage and disappeared 6 months later. EBER (EBV-encoded small RNA) were identified in the gastric mucosa by in situ hybridization 24 hours after the gavage and it lasted for 9 months. EBER positive adenocarcinoma were developed in the stomach 9 months after the gavage of EBV.In the next experiment, Balb/c nude mice (6-7W and 10 month, n=10 each) were used to evaluate the carcinogenesis of GTC-5-EBV. GTC-5-EBV was injected weekly for 8 times. After 4 months, adenocarcinoma were found in the rectum of 100 % of elderly mice. In contrast, no cancer was found in the young mice during the observation period of 6 months.Our model of EBV associated carcinogenisis of digestive tract seems useful in studying the etiology and treatment of EBV associated disorders.