Effects of serum starvation on radiosensitivity, proliferation and apoptosis in four human tumor cell lines with different p53 status.
OBJECTIVE
The effects of serum starvation on radiation sensitivity, cell proliferation and apoptosis were investigated with particular consideration of the p53 status.


METHODS
Four human tumor cell lines, Be11 (melanoma, p53 wild-type), MeWo (melanoma, p53 mutant), 4197 (squamous cell carcinoma, p53 wild-type) and 4451 (squamous cell carcinoma, p53 mutant), were used. After the cells had been incubated in starvation medium (0.5% FCS) for 1-6 days, changes in cell cycle distribution, induction of apoptosis and necrosis, and changes in radiation sensitivity were assessed by two-parameter flow cytometric measurements of DNA-dye-exclusion/Annexin V binding, and a conventional colony assay, respectively.


RESULTS
p53 wild-type cell lines showed a decrease in the BrdU labeling index and an increase in the apoptotic cell frequency in starvation medium. p53 mutant cell lines showed a decrease in the BrdU labeling index but no evidence of apoptosis. These cells went into necrosis instead. The radiation sensitivity was increased in 4451 and slightly decreased in Be11 and 4197 in starvation medium.


CONCLUSIONS
These data suggest a functional involvement of p53 in starvation-induced G1-block and apoptosis in tumor cells. Altered radiosensitivity after culture in starvation medium seemed to be explained at least in part by the starvation-induced G1-block. The frequency of starvation-induced apoptosis or necrosis was not correlated with radiation sensitivity.
Oya
Natsuo
N
Institute for Medical Radiation Biology, University Hospital Essen, Germany. oya@kuhp.kyoto-u.ac.jp
Zölzer
Friedo
F
Werner
Frank
F
Streffer
Christian
C
D017304:Annexin A5 / Q000032:analysis; D017209:Apoptosis / Q000528:radiation effects; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy; D002453:Cell Cycle / Q000528:radiation effects; D003470:Culture Media; D003627:Data Interpretation, Statistical; D004307:Dose-Response Relationship, Radiation; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000532:radiotherapy; D006801:Humans; D008545:Melanoma / Q000532:radiotherapy; D009154:Mutation; D009369:Neoplasms / Q000532:radiotherapy*; D011829:Radiation Dosage; D011836:Radiation Tolerance; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D017304:Annexin A5; D003470:Culture Media; D016159:Tumor Suppressor Protein p53