Abstract
Balb/c nude mice were subcutaneously transplanted with fetal nasopharyngeal mucosa infected with B95-8 Epstein-Barr virus (EBV). n-Butyrate and/or 12-O-tetradecanoylphorbol 13-acetate (TPA) were injected subcutaneously on the third day and once a week thereafter. About 10 days later, tumor masses gradually grew in these mice. Histopathological examination was carried out 15 weeks later. Three cases of lymphomas (two T cell lymphomas and one B cell lymphoma) were observed in the group receiving EBV and TPA, and one T cell lymphoma and three cases of undifferentiated carcinoma were found in the group receiving EBV, TPA and n-butyrate, but no case was found in the control groups that were transplanted with fetal nasopharyngeal tissue infected with EBV, or TPA and n-butyrate alone. Polymerase chain reaction amplification and in situ hybridization revealed that lymphoma and carcinoma cells contained the EBV LMP1 and EBERs genes. LMP1 protein was also found in the carcinoma. The T and B cell lymphomas and the nasopharyngeal carcinoma in nude mice were derived from human nasopharyngeal mucosa; this was proved by using human specific monoclonal antibodies to CD3 for T cells, to CD20 for B cells, and to epithelial membrane antigen for epithelial cells. Nucleotide sequence analysis indicated that the homologies of EBV LMP1 genes in the induced malignant lymphomas and undifferentiated carcinomas to the B95-8 cell gene were around 96% and 99% respectively. The results showed that EB virus can infect nasopharyngeal mucosa of the human fetus and consequently induce malignant transformation by the synergistic effect of the tumor promoters, and that EBV DNA can persist in the lymphomas and carcinomas.
Similar content being viewed by others
Author information
Authors and Affiliations
Additional information
Received: 6 April 1998 / Accepted: 25 June 1998
Rights and permissions
About this article
Cite this article
Liu, Z., Liu, Y. & Zeng, Y. Synergistic effect of Epstein-Barr virus and tumor promoters on induction of lymphoma and carcinoma in nude mice. J Cancer Res Clin Oncol 124, 541–548 (1998). https://doi.org/10.1007/s004320050212
Issue Date:
DOI: https://doi.org/10.1007/s004320050212