Gene expression profiling of breast cells induced by X-rays and heavy ions

Abstract

Abstract. Several genetic aberrations and gene expression changes have been shown to occur when cells are exposed to various types of radiation. The integrity of DNA depends upon several processes that include DNA damage recognition and repair, replication, transcription and cell cycle regulation. Ionizing radiation has many sources, including radon decay from the soil and X-rays from medical practice. Epidemiological evidence indicates a risk for cancer by inducing genetic alterations through DNA damage, and molecular alterations have been reported in epidemiological studies of the A-bomb survivors. A spontaneously immortalized human breast epithelial cell model, MCF-10F, was used to examine the gene expression profiling of breast cells induced by X-ray and heavy ion exposure, by a cDNA expression array of DNA damage and repair genes. This cell line was exposed to 10, 50, 100 and 200 cGy of either X-rays or heavy ions and gene expression profiles were studied. Results indicated that out of a total of 161 genes, 38 were differentially expressed by X-ray treatment and 24 by heavy ion (Fe +2 ) treatment. Eight genes were common to both treatments and were confirmed by Northern blot analysis: BRCA1, BIRC2/CIAP1, CENP-E, DDB1, MRE11A, RAD54/ATRX, Wip1 and XPF/ERCC4. A number of candidate genes reported here may be useful molecular biomarkers of radiation exposure in breast cells.

Genetic Variants in DNA Repair Predicts the Survival of Patients with Esophageal Cancer

“…21 As an important NER molecules associating with ERCC1, ERCC4 expression was found to be upregulated after exposure to irradiation, in breast cancer cell or tumor of the patients with cervical cancer. 26,38 Cells defective in the ERCC4/ERCC1 can be unusually sensitive to hypoxic iraadiation via impairment of repair for DNA cross link damage. 27 The ERCC4 rs3136038 polymorphism is located within the promoter region near the starting codon of ERCC4.…”

Transcriptional regulation of human DNA repair genes following genotoxic stress: trigger mechanisms, inducible responses and genotoxic adaptation

“…DDB1 : Transcriptional activation of DDB1 was shown to be induced by ionizing radiation in MCF10F human breast epithelial cells, leading to enhanced expression of mRNA (11). No evidence was provided, however, for an upregulation of the protein.…”

Genome-Wide Expression Changes in Saccharomyces cerevisiae in Response to High-LET Ionizing Radiation

“…Our results suggest that ionizing irradiation causes DNA damage in yeast regardless of specific LET IR type. DNA damage caused by both high-and low-LET IR has also been reported in human cells [7,[49][50][51]. The YNL194c gene product when expressed as a GFP fusion protein has been shown to be induced in response to the DNA-damaging agent MMS [52].…”