Implication of PBP74/mortalin/GRP75 in the radio-adaptive response.
OBJECTIVE
To investigate the relationship between expression of the human peptide-binding protein PBP74 and the occurrence of an adaptive response to ionizing radiation.


METHODS
Human tumour cell lines HT29 and MCF-7 were transfected with a PBP74 or PBP74 antisense construct. For demonstration of an adaptive response, cells lines were irradiated with a conditioning dose of 0.25 Gy cobalt-60 gamma-rays followed by a second dose of 4.0 Gy after an interval of 4.5 h. Response was measured in terms of clonogenic survival.


RESULTS
Transfection of a PBP74 plasmid caused transient overexpression of PBP74 mRNA in both cell lines. The optimal dose for the induction of PBP74 in the cell lines investigated was 0.1-0.25Gy and PBP74 induction occurred within 30 min of irradiation. For both cell lines, the adaptive response was repressed when cells were transfected with the anti-PBP plasmid. However, the converse, an enhancement of the adaptive response in cell lines transfected with the PBP74 construct, was seen only for HT29 cells under certain experimental conditions.


CONCLUSIONS
The results support the view that while PBP74 is necessary to the adaptive response, it may not by itself be sufficient for the adaptive response to occur.
Carette
J
J
Department of Oncology, McGill University, Montréal, Québec, Canada.
Lehnert
S
S
Chow
T Y-K
TY
D000222:Adaptation, Physiological / Q000235:genetics / Q000528:radiation effects; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology; D004249:DNA Damage; D004260:DNA Repair; D015870:Gene Expression / Q000528:radiation effects; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000502:physiology; D019073:HT29 Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D024101:Mitochondrial Proteins; D009369:Neoplasms / Q000235:genetics / Q000503:physiopathology / Q000532:radiotherapy*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D011836:Radiation Tolerance / Q000235:genetics / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D018840:HSP70 Heat-Shock Proteins; C492001:HSPA9 protein, human; C083794:Hspa9 protein, mouse; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C018551:glucose-regulated proteins; C080352:mortalin