title: Gene expression profiles of normal human fibroblasts after exposure to ionizing radiation: a comparative study of low and high doses.
abstract: Several types of cellular responses to ionizing radiation, such as the adaptive response or the bystander effect, suggest that low-dose radiation may possess characteristics that distinguish it from its high-dose counterpart. Accumulated evidence also implies that the biological effects of low-dose and high-dose ionizing radiation are not linearly distributed. We have investigated, for the first time, global gene expression changes induced by ionizing radiation at doses as low as 2 cGy and have compared this to expression changes at 4 Gy. We applied cDNA microarray analyses to G1-arrested normal human skin fibroblasts subjected to X irradiation. Our data suggest that both qualitative and quantitative differences exist between gene expression profiles induced by 2 cGy and 4 Gy. The predominant functional groups responding to low-dose radiation are those involved in cell-cell signaling, signal transduction, development and DNA damage responses. At high dose, the responding genes are involved in apoptosis and cell proliferation. Interestingly, several genes, such as cytoskeleton components ANLN and KRT15 and cell-cell signaling genes GRAP2 and GPR51, were found to respond to low-dose radiation but not to high-dose radiation. Pathways that are specifically activated by low-dose radiation were also evident. These quantitative and qualitative differences in gene expression changes may help explain the non-linear correlation of biological effects of ionizing radiation from low dose to high dose.
authors.affiliation: Lawrence Berkeley National Laboratory, Life Sciences Division, Berkeley, California, 94720, USA.
authors.forename: Liang-Hao
authors.initials: LH
authors.lastname: Ding
authors.forename: Masato
authors.initials: M
authors.lastname: Shingyoji
authors.forename: Fanqing
authors.initials: F
authors.lastname: Chen
authors.forename: Jeng-Jong
authors.initials: JJ
authors.lastname: Hwang
authors.forename: Sandeep
authors.initials: S
authors.lastname: Burma
authors.forename: Clarissa
authors.initials: C
authors.lastname: Lee
authors.forename: Jan-Fang
authors.initials: JF
authors.lastname: Cheng
authors.forename: David J
authors.initials: DJ
authors.lastname: Chen
mesh_terms: D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology* / Q000528:radiation effects*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020543:Proteome / Q000378:metabolism*; D011829:Radiation Dosage; D011839:Radiation, Ionizing; D012867:Skin / Q000187:drug effects / Q000378:metabolism
chemical_list: D020543:Proteome