Chromosomal localization of the transcription factor YY1 in the mouse and human

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47010/1/335_2004_Article_BF00360552.pd

Low Dose Radiation Induced Transcriptional Alterations in Directly Irradiated and Bystander Fibroblast Cells

Introduction: Formerly, we studied transcriptional alterations in primary human fibroblast cells after irradiation with 2 Gy (Kis et al. Int J Radiat Oncol Biol Phys. 66:1506-14. 2006). We found that about 200 genes responded to radiation and the expression profile depended on individual genetic backgrounds. Thirty consensus radiation response genes answered to radiation in identical manner in all investigated cells. Now, we have investigated low dose radiation induced transcriptional responses in directly hit and bystander cells. Methods: F11 primary human fibroblasts were irradiated with different doses (10, 40, 100 and 500 mGy) of 60Co gamma radiation. To investigate radiation-induced transcriptional alterations in directly irradiated cells, RNA was isolated 2 h after irradiation. To study responses in bystander cells the culture medium was removed from the irradiated cells 2 h after irradiation and transferred to unirradiated recipient cells. RNA was isolated 2 h later and the transcriptional profile analyzed by whole genome microarrays. Results: When cells were irradiated with 500 mGy 1119 genes responded to radiation. Ten of the formerly identified consensus radiation response genes changed its transcription (CDKN1A, TP53INP1, CYP26B1, BTG2, BBC3, PPM1D, THSD1, GDF15, NM_024661, BC010544). Irradiation of F11 fibroblasts with 100 and 10 mGy altered the transcription profile of 847 and 1414 genes, respectively. When we compared the transcription profile of cells irradiated with 500 and 100 mGy 377 similar alterations were detected, among them 6 consensus radiation response genes (CDKN1A, TP53INP1, GDF15, BTG2, BBC3, NM_024661) changed its transcription in an identical manner. One hundred and twenty-four genes responded to radiation after all applied doses. In bystander cells 655 and 406 genes responded to 500 and 100 mGy irradiations, respectively on the transcription level. After irradiation with 40 and 10 mGy the number of responding genes were 152 and 619, respectively. When we compared the responses in bystander cells after irradiation with 100 and 40 mGy only 40 genes responded identically. The comparison of the transcriptional profile of 40 and 10 mGy irradiated cells detected 60 similar responses. Altogether fifteen genes responded to all doses of radiation in bystander cells. Finally, we have detected nine genes (DLGAP4, HRASLS5, TMEM167, RPL23, RPL38, PRSS36, and three hypothetical proteins) responding to all doses of radiation both in directly irradiated and bystander cells. Conclusions: By the analysis of radiation induced transcriptional alterations one might find potential biomarkers suitable to detect low dose responses

Effects of Low Dose Radiation on the Main Immune Parameters in Healthy Mice

Objectives: We investigated the effect of low dose ionizing radiation on the quantitative and qualitative changes of major immune parameters in healthy mice. Methods: To study radiation effects on various lymphocyte subsets, mice were irradiated with different acute doses (0.01, 0.05, 0.1, 0.5, 1, 2 and 4 Gy) of Co60-? rays. Animals were killed at different time points after irradiation, and splenocytes were isolated. Quantitative and functional changes were determined in the Thelper (CD3+CD4+), Tcytotoxic (CD3+CD8+), Treg (CD4+CD25+), NK (NK1.1+) and DC (MHCII+CD11c+) cells. The ratio of various lymphocyte subsets was determined by flow cytometry. The apoptotic rate of the cells was determined by TUNEL assay 4 hours after the in vivo irradiation of the animals. The proliferative response of lymphocytes to non-specific stimuli (Concanavalin A) was determined. The T-cell activation potential of irradiated DCs was studied in mixed lymphocyte culture. Cytokine expression of irradiated lymphocytes was investigated by real-time RT-PCR. Results: Flow cytometry data show that low dose irradiation affects the main compartments of T-cell immunity, but ample differences exist in the radiosensitivity of various cellular compartments, with the CD3+CD8+ compartment being the most radiosensitive and the CD4+CD25+ compartment being the most radioresistant. Certain lymphocyte subsets presented hypersensitivity to radiation at low doses (10, 50 and 100 mGy). The proliferation rate of ConA stimulated lymphocytes was either not affected or slightly depressed after irradiation with low doses. Higher doses led to a marked decrease in lymphocyte proliferation. Spontaneous apoptosis rate was around 3% and doses up to 0.1 Gy did not change apoptosis frequency. A steep increase in the apoptotic rate was detected after irradiation with doses of 0.5 Gy or above. The capacity of splenic DCs to activate allogeneic T cells was investigated three days after the irradiation of the animals. Preliminary data showed, that an increased T cell activation could be detected, if DCs were irradiated with low doses. The ratio of IFN-? expression in the ConA stimulated versus unstimulated lymphocytes showed a dose-dependent decrease. Conclusion: The experiments suggest that even low doses of ionizing radiation might have substantial impact on various compartments of the immune system. Different lymphocyte subpopulations react in very different ways to irradiation, which clearly point to a heterogeneous radiation response of the immune cells mostly involved in the anti-tumor immune response

Induced acute erythema and late pigmentation may not be correlated: In regards to Perera et al. (Int J Radiat Oncol Biol Phys 2005;62:1283-1290)

peer reviewed[No abstract available

Age-related effects of X-ray irradiation on mouse hippocampus.

Therapeutic irradiation of pediatric and adult patients can profoundly affect adult neurogenesis, and cognitive impairment manifests as a deficit in hippocampal-dependent functions. Age plays a major role in susceptibility to radiation, and younger children are at higher risk of cognitive decay when compared to adults. Cranial irradiation affects hippocampal neurogenesis by induction of DNA damage in neural progenitors, through the disruption of the neurogenic microenvironment, and defective integration of newborn neurons into the neuronal network. Our goal here was to assess cellular and molecular alterations induced by cranial X-ray exposure to low/moderate doses (0.1 and 2 Gy) in the hippocampus of mice irradiated at the postnatal ages of day 10 or week 10, as well as the dependency of these phenomena on age at irradiation. To this aim, changes in the cellular composition of the dentate gyrus, mitochondrial functionality, proteomic profile in the hippocampus, as well as cognitive performance were evaluated by a multidisciplinary approach. Our results suggest the induction of specific alterations in hippocampal neurogenesis, microvascular density and mitochondrial functions, depending on age at irradiation. A better understanding of how irradiation impairs hippocampal neurogenesis at low and moderate doses is crucial to minimize adverse effects of therapeutic irradiation, contributing also to radiation safety regulations