title: Micro RNA responses to chronic or acute exposures to low dose ionizing radiation.
abstract: Human health risks of exposure to low dose ionizing radiation remain ambiguous and are the subject of intense debate. A wide variety of biological effects are induced after cellular exposure to ionizing radiation, but the underlying molecular mechanism(s) remain to be completely understood. We hypothesized that low dose γ-radiation-induced effects are controlled by the modulation of micro RNA (miRNA) that participate in the control of gene expression at the posttranscriptional level and are involved in many cellular processes. We monitored the expression of several miRNA in human cells exposed to acute or chronic low doses of 10 cGy or a moderate dose of 400 cGy of (137)Cs γ-rays. Dose, dose rate and time dependent differences in the relative expression of several miRNA were investigated. The expression patterns of many miRNA differed after exposure to either chronic or acute 10 cGy. The expression of miRNA let-7e, a negative regulator of RAS oncogene, and the c-MYC miRNA cluster were upregulated after 10 cGy chronic dose but were downregulated after 3 h of acute 10 cGy. The miR-21 was upregulated in chronic or acute low dose and moderate dose treated cells and its target genes hPDCD4, hPTEN, hSPRY2, and hTPM1 were found to be downregulated. These findings provide evidence that low dose and dose rate γ-irradiation dictate the modulation of miRNA, which can result in a differential cellular response than occurs at high doses. This information will contribute to understanding the risks to human health after exposure to low dose radiation.
authors.affiliation: Department of Medical Laboratory and Radiation Sciences, University of Vermont, 302 Rowell Building, Burlington, VT 05405, USA. mchaudhr@uvm.edu
authors.forename: M Ahmad
authors.initials: MA
authors.lastname: Chaudhry
authors.forename: Romaica A
authors.initials: RA
authors.lastname: Omaruddin
authors.forename: Bridget
authors.initials: B
authors.lastname: Kreger
authors.forename: Sonia M
authors.initials: SM
authors.lastname: de Toledo
authors.forename: Edouard I
authors.initials: EI
authors.lastname: Azzam
mesh_terms: D002460:Cell Line; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000528:radiation effects*; D011829:Radiation Dosage; D012867:Skin / Q000166:cytology / Q000528:radiation effects; D015533:Transcriptional Activation
chemical_list: D035683:MicroRNAs