Project description:In recent years there is a growing epidemiological indication of excess risk of cardiovascular disease at low doses of ionizing radiation without a clear-cut threshold. It is proposed that damage to the vascular endothelium is critical in radiation-related cardiovascular diseases. In order to identify and better understand the underlying molecular mechanisms of ionizing radiation on endothelial cells, we performed a microarray analysis on immortalized human coronary artery endothelial cells irradiated with different doses (0.00, 0.05, 0.10, 0.50 and 2.0 Gy). RNA was extracted at different time points after irradiation (1 day, 7 days, 14 days).
Project description:Although major differences in the response of tissues were documented in the literature, the molecular mechanisms underlying tissue radiosensitivity are still fragmentary and need to be study more thoroughly. To this end, a genome wide analysis strategy was used to investigate changes in gene expression in the liver following exposition to ionizing radiation. This follows the tissue survey that was previously initiated with other organs and tends to obtain a comprehensive picture of the molecular events underlying tissue radio sensitivity. Keywords: Ionizing radiation response
Project description:gDNA from patient samples with multiple basal cell carcinomas and possible exposure to ionizing radiation was hybridized Vs. GM12878 gDNA to assess CNAs. We aimed to find a possible common aberration pattern related to ionizing radiation or a rare metastasis.
Project description:Tardigrades can survive remarkable doses of ionizing radiation, up to about 1000 times the lethal dose for humans. How they do so is incompletely understood. We found that the tardigrade Hypsibius exemplaris suffers DNA damage upon gamma irradiation, but damage is repaired. We show that tardigrades have a specific and robust response to ionizing radiation: irradiation induces a rapid, dramatic upregulation of many DNA repair genes. By expressing tardigrade genes in bacteria, we validate that increased expression of some repair genes can suffice to increase radiation tolerance. We show that at least one such gene is necessary for tardigrade radiation tolerance. Tardigrades’ ability to sense ionizing radiation and massively upregulate specific DNA repair pathway genes may represent an evolved solution for maintaining DNA integrity.
Project description:Densely ionizing radiation is a major component of the space radiation environment and has potentially greater carcinogenic effect compared to sparsely ionizing radiation that is prevalent in the terrestrial environment. It is unknown to what extent the irradiated microenvironment contributes to the differential carcinogenic potential of densely ionizing radiation. To address this gap, 10-week old BALB/c mice were irradiated with 100 cGy sparsely ionizing g-radiation or 10, 30, or 80 cGy of densely ionizing, 350 MeV/amu Si particles and transplanted 3 days later with syngeneic Trp53 null mammary fragments. Tumor appearance was monitored for 600 days. Tumors arising in Si-particle irradiated mice had a shorter median time to appearance, grew faster and were more likely to metastasize. Most tumors arising in sham-irradiated mice were ER-positive, pseudo-glandular and contained both basal keratin 14 and luminal keratin 8/18 cells (designated K14/18), while most tumors arising in irradiated hosts were K8/18 positive (designated K18) and ER negative. Comparison of K18 vs K14/18 tumor expression profiles showed that genes increased in K18 tumors were associated with ERBB2 and KRAS while decreased genes overlapped with those down regulated in metastasis and by loss of E-cadherin. Consistent with this, K18 tumors grew faster than K14/18 tumors and more mice with K18 tumors developed lung metastases compared to mice with K14/18 tumors. However, K18 tumors arising in Si-particle irradiated mice grew even faster and were more metastatic compared to control mice. A K18 Si-irradiated host profile was enriched in genes involved in mammary stem cells, stroma, and Notch signaling. Thus systemic responses to densely ionizing radiation enriches for a ER-negative, K18-positive tumor, whose biology is more aggressive compared to similar tumors arising in non-irradiated hosts. Key Words: ionizing radiation; breast cancer; heavy ion radiation;initiation; promotion
Project description:Although major differences in the response of tissues were documented in the literature, the molecular mechanisms underlying tissue radiosensitivity are still fragmentary and need to be study more thoroughly. To this end, a genome wide analysis strategy was used to investigate changes in gene expression in the liver following exposition to ionizing radiation. This follows the tissue survey that was previously initiated with other organs and tends to obtain a comprehensive picture of the molecular events underlying tissue radio sensitivity. Keywords: Ionizing radiation response totalRNA sample from irradiated liver was hybridized against totalRNA sample from non-irradiated liver. 8 dye-swaps have been done.