Radiation-induced gene expression in MCF-7 cells.
OBJECTIVE
Detection of gene targets applicable to biological dosimetry and early detection of radiation-induced cell damage.


METHODS
MCF-7 human mammary carcinoma cells were exposed to 2 and 6 Gy X-rays. Expression of 1176 genes was traced with the Atlas Human 1.2 Array (Clontech).


RESULTS
(1) Based on data reproducibility (about 98%), a new and improved analysis was employed. (2) Normalization of data using ubiquitin or total gene expression led to the same results. (3) Dose-dependent gene expression was shown for six genes, which were constantly expressed over 1 day (three genes), 2 days (two) and 3 days (one). Differential gene expression was confirmed by RTQ-PCR. Three of the six genes were novel radiation-induced gene targets. (4) When analysing the expression of all genes, the processes of cell degradation (e.g. cell death and protein catabolism) were activated. Simultaneously, inhibition not only of cell proliferation, but also of other cellular functions (e.g. cell repair) was found. Hence, cell death appears a process of 'active silencing'.


CONCLUSIONS
With the screening method applied, six radiation-induced gene targets were found, three of which were novel genes. Their applicability in other cell models remains to be tested. Different sets of genes have to be considered for dose assessment, owing to their changes in gene expression with time after irradiation. Furthermore, it has to be investigated whether 'active silencing' represents a general principle of radiation-induced cell death.
Stassen
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Institute of Radiobiology of the German Armed Forces, Neuherbergstr. 11, D-80937 Munich, Germany.
Port
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Nuyken
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Abend
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D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy*; D016923:Cell Death / Q000528:radiation effects; D004273:DNA, Neoplasm / Q000235:genetics; D004307:Dose-Response Relationship, Radiation; D005260:Female; D015870:Gene Expression / Q000528:radiation effects*; D020869:Gene Expression Profiling / Q000706:statistics & numerical data; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011836:Radiation Tolerance; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins