Functional inactivation of p53 by HPV-E6 transformation is associated with a reduced expression of radiation-induced potentially lethal damage.
OBJECTIVE
To examine the effect of functional loss of p53 on radiation sensitivity and potentially lethal damage repair (PLDR).


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 plateau-phase 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.
Schwartz
J L
JL
Department of Radiation Oncology, University of Washington, Seattle 98195, USA.
Rasey
J
J
Wiens
L
L
Jordan
R
R
Russell
K J
KJ
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology / Q000821:virology*; D002470:Cell Survival / Q000528:radiation effects; D002472:Cell Transformation, Viral / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D016158:Genes, p53; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology*; D009381:Neoplasms, Radiation-Induced / Q000235:genetics / Q000473:pathology / Q000821:virology; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D027383:Papillomaviridae / Q000235:genetics*; D011836:Radiation Tolerance; D012097:Repressor Proteins; D014407:Tumor Cells, Cultured
C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins