The Insertion of Foreign DNA Into Mammalian Genomes and Its Consequences: A Concept in Oncogenesis

Abstract

Publisher Summary This chapter examines the consequences of foreign deoxyribonucleic acid (DNA) insertion into established mammalian genomes. In mammalian cells, the ever-present repetitive DNA sequences possibly constitute a reservoir of insertion targets whose disturbance may have less immediate functional consequences. Among the consequences of the insertion of foreign DNA into the established genomes and of the transformed cell phenotype are the de novo methylation of the foreign DNA and alterations in the existing patterns of DNA methylation in the preexisting cellular genome. Diet-ingested foreign DNA could play an important role in eliciting mutagenic and oncogenic events in mammals. In light of these findings, the postulated cellular defense mechanism by methylation of integrated foreign DNA becomes plausible. The results of studies on the model of adenovirus DNA integration in mammalian cells suggested that the insertion of foreign DNA had to be rather pliable. There is a possibility that the insertion of foreign DNA into an established mammalian genome can lead to far-reaching alterations in the patterns of cellular DNA methylation and gene expression. The classical concept of insertional mutagenesis relates to damage caused to cellular functions or genes that are encoded at the sites of foreign (adenoviral) DNA insertion into the host genome.