Introduction of uv-damaged dna into human tumour cells increases clonogenic survival following cisplatin treatment at low doses

A major obstacle in achieving a positive clinical outcome using platinumbased chemotherapy is the development of tumours with an acquired drug resistance. This has made the mechanisms by which tumour cells become drug resistant the object of intense clinical and biological investigation, DNA damaging agents like cisplatin, lV light and ionizing radiation, induce a number of cellular responses including acquired resistance, increased capacity for DNA repair, eel! cycle arrest and apoptosis. One stimulus which causes these responses is thought to involve the presence or the persistence of damaged DNA in (he nucleus. In order to study the effects caused specifically by the presence of damaged DNA in the nucleus, we have used a non-replicating, recombinant ademtvirus (Ad) to deliver cither damaged or undamaged DNA into SCC-25 human carcinoma cells. Cells were infected with either UV-irradiated or unirradiated Ad and then seeded at low density, treated with cisplatin and assessed for clonogenk survival. We report here that cells infected with UV-irradiated Ad showed an increased resistance to cisplatin at low doses compared to cells infected with unirradiated virus. It is possible that the introduction of exogenous, UV-damaged DNA into human carcinoma cells triggers a cellular response whidi modulates the extent of cellular DNA damage and/or DNA repair following low dose cisplatin treatment.