Functional inactivation of p53 by HPV-E6 transformation is associated with a reduced expression of radiation-induced potentially lethal damage

Abstract

Purpose : To examine the effect of functional loss of p53 on radiation sensitivity and potentially lethal damage repair (PLDR). Materials and methods : Radiation sensitivity and PLDR were examined in an isogenic pair of human tumour cell lines created by HPV- E6 transformation. Results : Inactivation of p53 by E6 transformation resulted in a cell line that was more resistant to killing by radiation but showed little enhancement in survival (PLDR) when plateauphase cells were held non-cycling after radiation exposure. Holding p53 -normal cells in plateau-phase after radiation exposure not only led to enhanced survival, but also to a reduction in the proportion of cells that blocked in G1 subsequent to release. Conclusions : These results suggest that p53 expression influences that component of radiation sensitivity associated with PLDR.