Alterations in DNA repair efficiency are involved in the radioresistance of esophageal adenocarcinoma.
To study radioresistance in esophageal adenocarcinoma, we generated an isogenic cell line model by exposing OE33 esophageal adenocarcinoma cells to clinically relevant fractionated doses of radiation (cumulative dose 50 Gy). A clonogenic assay confirmed enhanced survival of the radioresistant OE33 subline (OE33 R). To our knowledge, we are the first to generate an isogenic model of radioresistance in esophageal adenocarcinoma. This model system was characterized in terms of growth, cell cycle distribution and checkpoint operation, apoptosis, reactive oxygen species generation and scavenging, and DNA damage. While similar properties were found for both the parental OE33 (OE33 P) cells and radioresistant OE33 R cells, OE33 R cells demonstrated greater repair of radiation-induced DNA damage. Our results suggest that the radioresistance of OE33 R cells is due at least in part to increased DNA repair.
Department of Surgery, Trinity College Dublin, Trinity Centre for Health Sciences, St. James's Hospital, Dublin 8, Ireland.
Niamh
N
Lynam-Lennon
John V
JV
Reynolds
Graham P
GP
Pidgeon
Joanne
J
Lysaght
Laure
L
Marignol
Stephen G
SG
Maher
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D017209:Apoptosis / Q000528:radiation effects; D002453:Cell Cycle / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D004260:DNA Repair; D004938:Esophageal Neoplasms / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D006657:Histones / Q000032:analysis; D006801:Humans; D011836:Radiation Tolerance; D017382:Reactive Oxygen Species / Q000378:metabolism
C468783:H2AX protein, human; D006657:Histones; D017382:Reactive Oxygen Species