Adenovirus oncogenesis: alterations in cellular methylation and transcription patterns− factors in viral oncogenesis?

Abstract

My laboratory has been interested in the consequences of the insertion of foreign DNA into established mammalian genomes and has studied this problem in adenovirus type 12 (Ad12)-transformed cells or in Ad12-induced hamster tumors. Ad12 is a potent oncogenic agent in newborn Syrian hamsters. Since integrated foreign genomes are frequently de novo methylated, it appears that they might be modified by an ancient defense mechanism against foreign DNA. In cells transgenic for the DNA of Ad12 or for the DNA of bacteriophage λ, changes in cellular methylation and transcription patterns have been observed. Thus, the insertion of foreign DNA can have important functional consequences which are not limited to the site of foreign DNA insertion. These findings appear to be relevant also for viral oncology, tumor biology and for the interpretation of data derived from transgenic organisms. For most animals, the main portal of entry for foreign DNA is the gastrointestinal tract. We have investigated the fate of orally ingested foreign DNA in mice. Naked DNA of bacteriophage M13 or the cloned gene for the green fluorescent protein (GFP) of Aequorea victoria have been used as test molecules. At least transiently, food-ingested DNA can be traced to different organs and, after transplacental transmission, to fetuses and newborns. There is no evidence for germ line transmission or for the expression of orally administered GFP DNA.