Viral-induced human carcinogenesis: an oxidative stress perspective

Oncogenic transformation occurs via many different mechanisms. Alterations in the expression of certain key genes (oncogenes and/or tumor suppressor genes) contribute to the development of the tumorigenic state of uncontrolled cell proliferation. Tumor viruses' studies have contributed over the last 2 decades significantly in cancer etiology, first by providing valuable information on the mechanisms and dissection of cell signaling and growth control pathways and second by being causative agents of human neoplasia. Viruses contribute to the development of the neoplastic state through many mechanisms: inactivation of tumor suppressor genes, hyperstimulation of cellular proto-oncogene transcription, or by viral protein interference with the cellular transcription, signal transduction, DNA repair and apoptosis pathways and induction of chronic oxidative stress. On the other hand, only recently research has provided evidence of the epigenetic pathway involvement and especially the DNA methylation machinery. To this end, both hypomethylation-induced oncogenic activation and/or hypermethylation-induced tumor suppressor gene silencing are linked with viral-induced carcinogenesis. In this review, we discuss the current status of knowledge on viral-associated carcinogenesis with emphasis on the mechanisms of oxidative stress and DNA damage induction in humans by viruses as well as implications in cancer treatment.