Mouse Endogenous Retroviral Long Terminal Repeat (LTR) Elements and Environmental Carcinogenesis

摘要

For the past several years, the working hypothesis of this laboratory has been that chromosomal retrovirus-related gene elements play important roles in gene-rearrangement and gene-activation events of carcinogenesis and mutagenesis induced by environmental agents. This working hypothesis is based on the concept of transposable genes as well as the recent understanding of retroviruses (RNA tumor viruses) in relation to the carcinogenesis problem. Activation of transposable gene elements has been discussed from the viewpoint of unprogrammed genomic changes in response to unanticipated genomic shocks. This view was used in considering the possibility of transposable gene elements involved in genetic changes of cancer formation in the animal. In this regard, this concept is similar to the perspectives of RNA tumor viruses, the oncogene-virogene hypothesis, and the provirus hypothesis because retroviruses replicate through DNA forms that carry long terminal repeat (LTR) sequences resembling the insertion sequences (or the IS elements) of prokaryotic transposons. The finding of oncogene myc activation in avian leukosis virus-induced leukemogenesis and proviral insertion in the mouse dilute locus mutation have also pointed to the functional similarity between retroviruses and transposable genes. (ERA citation 14:006443)