Understanding the mechanisms producing low dose ionizing radiation specific biological effects represents one of the major challenges of radiation biology. Although experimental evidence does suggest that various molecular stress response pathways may be involved in the production of low dose effects, much of the detail of those mechanisms remains elusive. We hypothesized that the regulation of various stress response pathways upon irradiation may differ from one another in complex dose-response manners, causing the specific and subtle low dose radiation effects. In the present study, the transcription level of 22 genes involved in stress responses were analyzed using RT-qPCR in normal human fibroblasts exposed to a range of gamma-doses from 1 to 200 cGy. Using the alkali comet assay, we also measured the level of DNA damages in dose-response and time-course experiments. We found non-linear dose responses for the repair of DNA damage after exposure to gamma-radiation. Alterations in gene expression were also not linear with dose for several of the genes examined and did not follow a single pattern. Rather, several patterns could be seen. Our results suggest a complex interplay of various stress response pathways triggered by low radiation doses, with various low dose thresholds for different genes.
BackgroundIonizing radiation in low doses is the ubiquitous environmental factor with harmful stochastic effects. Formaldehyde is one of the most reactive household and industrial pollutants. Dioxins are persistent organic pollutants and most potent synthetic poisons effective even at trace concentrations. Environmental pollutants are capable of altering the expression of a variety of genes. To identify the similarities and differences in the effects of low-dose ionizing radiation, formaldehyde and dioxin on gene expression, we performed the bioinformatic analysis of all available published data.ResultsWe found that that in addition to the common p53-, ATM- and MAPK-signaling stress response pathways, genes of cell cycle regulation and proinflammatory cytokines, the studied pollutants induce a variety of other molecular processes.ConclusionsThe observed patterns provide new insights into the mechanisms of the adverse effects associated with these pollutants. They can also be useful in the development of new bio-sensing methods for detection of pollutants in the environment and combating the deleterious effects.
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