Expression of the large T antigens of SV40 and Polyomavirus sensitizes normal human diploid fibroblasts to UV and cisplatin

OX A damaging agents induce accumulation and increased activitv of poof which is thought to lead to increased IA repair, cell cycle arrest and apoptosis. Although these responses are protective against transformation, the net effect of p53 dependant responses on cell survival is not entirely clear as t host1 outcomes have opposing effects. Cell cycle arrest appears to be mediated by transcriptional activation of the cyclin dependant kinase (cdk) inhibitor wafl which inhibits phosporylation of Rb. DNA tumour viruses encode a variety of proteins which disrupt p53 and/or Rb related proteins. Here we report the use of recombinant adenovirus constructs to transiently express the large tumour antigens of SV40 (SV40LT) and potyomavirus (PyLT) in order to evaluate the roie of Rb related proteins in resistance of normal human diploid fibroblasts to UV and cisplatin. These tumour antigens share significant homology and both are capable of immortalizing cells in culture. However. SV4ÖLT binds to both p53 and Rb related proteins whereas PyLT only binds to Rb family members. Expression of either SV40LT or PyLT sensitizes normal diploid fibroblasts to both UV and cisplatin. These results suggest that disruption of R.b related proteins can sensitize normal diploid cells to DNA damaging agents and further suggests that pRb mediated cell cycle arrest is protective against genotoxic stress. (Supported by NCI of Canada}.