Tumorigenicity and Organization of the Terminal Region of the Epstein-Barr Virus (EBV) Genome in LCLs Derived from Carcinogen-Treated Lymphocytes

Abstract

It has been proposed that uncontrolled EBV replication in the oral pharyngeal region is critical for the development of EBVassociated tumors. From epidemiological studies it seems certain that environmental cofactors contribute to the development of nasopharyngeal carcinoma (NPC). The recent discovery of carcinogen-inducible transcripts under the regulation of DNA damage-responsive elements provides a model to explain how DNA damage could influence viral expression and viral DNA replication (1–3). We propose that virus expression and viral DNA replication could be influenced by exposure to chemical or physical carcinogens through DNA damage-induced chromosomal decondensation followed by the direct interaction of carcinogen-inducible trans -acting factors with viral sequences homologous to DNA damage-responsive elements within the viral genome. Exposure to environmental carcinogens could result in the circumvention of normally stringent control of viral gene expression and lead to uncontrolled viral replication. These phenomena would account for an increase in tumors in populations exposed to viruses and environmental carcinogens.