Dominant genetic instability and sensitivity to DNA damaging agents in a mammalian cell line

An SV40 transformed Indian muntjac cell line (SVM) has been shown to be hypersensitive to cell killing by a wide range of DNA damaging agents. Evidence points to defects in DNA replication and DNA recombination resulting in chromosome instability both spontaneously and following exposure to DNA damaging agents. We have generated proliferating hybrids between SVM and a spontaneously transformed Indian muntjac cell line (DM). Study of these hybrids indicates that the SVM phenotype acts in a genetically dominant manner and is associated with the expression of SV40 large T antigen. We propose that transformation and immortalization of Indian muntjac fibroblasts by SV40 virus can lead to a set of persistent changes in gene expression that result in chromosome instability and increased sensitivity to DNA damaging agents. Genes involved in these processes are likely to be of great importance as chromosome instability can play a central role in cancer development.