[Effect of 0.1 Gy X-ray irradiation on gene expression profiles in normal human lymphoblastoid cells].

OBJECTIVE: To investigate the effect of 0.1 Gy X-ray irradiation on the gene expression profiles in normal human lymphoblastoid cells using gene microarray and to explore the possible mechanism of the biological effect of low-dose irradiation. METHODS: The NimbleGen 12×135 K microarray corresponding to 45033 genes was used to analyze the gene expression profiles in AHH-1 cells cultured for 6 h and 20 h after 0.1 Gy X-ray irradiation. A gene was identified as the differentially expressed gene if the ratio between its expression levels in irradiation group and control group was higher than 2 or lower than 0.5. RT-PCR and real-time PCR were used to confirm some differentially expressed genes. RESULTS: There were 760 up-regulated genes and 1222 down-regulated genes in the cells at 6 h after 0.1 Gy X-ray irradiation, while there were 463 up-regulated genes and 753 down-regulated genes at 20 h after 0.1 Gy X-ray irradiation; there were 92 differentially expressed genes in common. The expression of GADD45A, CDKN2A, and Cx43 measured using gene microarray was confirmed by RT-PCR and real-time PCR. CONCLUSION: Low-dose irradiation can affect the expression of many functional genes, which provides a basis for the research on the mechanism of radiation damage.

Assessment of radiation doses and DNA damage in pediatric patients undergoing interventional procedures for vascular anomalies.

Interventional procedures (IPs) have been widely used to treat vascular anomalies (VA) in recent years. However, patients are exposed to low-dose X-ray ionizing radiation (IR) during these fluoroscopy-guided IPs. We collected clinical information and IR doses during IPs and measured biomarkers including γ-H2AX, chromosome aberrations (CA), and micronuclei (MN), which underpin radiation-induced DNA damage, from 74 pediatric patients before and after IPs. For the 74 children, the range of dose-area product (DAP) values was from 1.2 to 1754.6 Gy∙cm2, with a median value of 27.1 Gy∙cm2. DAP values were significantly higher in children with lesions in the head and neck than in the limbs and trunk; the age and weight of children revealed a strong positive correlation with DAP values. The treated patients as a group demonstrated an increase in all three endpoints relative to baseline following IPs. Children with vascular tumors have a higher risk of dicentric chromosome + centric ring (dic+r) and cytokinesis-block micronucleus (CBMN) after IPs than children with vascular malformations. The younger the patient, the greater the risk of CA after IPs. Moreover, rogue cells (RCs) were found in five children (approximately 10%) after IPs, and the rates of dic+r and CBMN were significantly higher than those of other children (Z = -3.576, p < 0.001). These results suggest that there may be some children with VA who are particularly sensitive to IR, but more data and more in-depth experiments will be needed to verify this in the future.

[Establishment and verification of dose effect relation curves between T cell receptor gene mutation frequency and ionizing radiation dose].

OBJECTIVE: To establish the dose-effect curve between TCR MF and ionizing radiation. METHODS: Peripheral lymphocytes were collected from 8 healthy adults (4 males and 4 females) and cultured in vitro with 12 well culture plates. They were stimulated by PHA-P and IL-2 after exposed to different doses of irradiation (0.00 - 8.00 Gy) and cultured for 7 d. The dose-effect curve was established after measuring TCR MF using flow cytometry. Also, using the same method, we separated and cultured the peripheral lymphocytes collected from 16 radiotherapy cancer patients, whose radiation styles and doses were different, and then measured TCR MF to estimate the whole equivalent dose of radiotherapy patients through the dose-effect curve. Peripheral blood was collected and cultured, chromosome aberration (dicentric and ring) was determined under microscope to estimate irradiation dose. RESULTS: The relationship of dose-effect between the TCR MF and ionizing radiation (0.00 - 8.00 Gy) was well, the curve of large dose group (2.00 - 8.00 Gy), low dose group (0.00 - 1.00 Gy) and 0.00 - 8.00 Gy dose group were met with the quadratic polynomial model, the equation was TCR MF = -32.8579 + 20.5436D + 0.6341D(2), TCR MF = 1.796 + 0.017D + 5.155D(2) and TCR MF = -0.6229 + 6.305D + 0.6919D(2), respectively. D was the radiation dose (Gy). Using the established curve and the chromosome aberration method to estimate the systemic exposure dosage, the average relative deviation was 16.8%. CONCLUSION: The curve established by the TCR gene mutation analysis technology can be applied to exposure dose estimation of victims in ionization radiation accidents.

Xenon Exerts Neuroprotective Effects on Kainic Acid-Induced Acute Generalized Seizures in Rats via Increased Autophagy.

Xenon has been shown to have neuroprotective effects and is clinically used as a favorable safe inhalation anesthetic. We previously confirmed the neuroprotective effects of xenon treatment in epileptic animals. However, the mechanism underlying these protective effects remains unclear. We aimed to assess the effects of xenon inhalation on autophagy in neuronal injury induced by acute generalized seizures. Kainic acid (KA) was injected into the lateral ventricle of male Sprague-Dawley rats to induce acute generalized seizures. Next, the rats were treated via inhalation of a 70% xenon/21% oxygen/9% nitrogen mixture for 60 min immediately after KA administration. The control group was treated via inhalation of a 79% nitrogen/21% oxygen mixture. Subsequently, two inhibitors (3-methyladenine or bafilomycin A1) or an autophagy inducer (rapamycin) were administered, respectively, before KA and xenon administration to determine the role of autophagy in the protective effects of xenon. The levels of apoptosis, neuronal injury, and autophagy were determined in all the rats. Xenon inhalation significantly attenuated the severity of the seizure-induced neuronal injury. Increased autophagy accompanied this inhibitive effect. Autophagy inhibition eliminated these xenon neuroprotective effects. A simulation of autophagy using rapamycin recapitulated xenon's protective effects on KA-induced acute generalized seizures in the rats. These findings confirmed that xenon exerts strong neuroprotective effects in KA-induced acute generalized seizures. Further, they indicate that increased autophagy may underlie the protective effects of xenon. Therefore, xenon and autophagy inducers may be useful clinical options for their neuroprotective effects in epileptic seizures.

Assessment of Genomic Instability in Medical Workers Exposed to Chronic Low-Dose X-Rays in Northern China.

The increasing use of ionizing radiation (IR) in medical diagnosis and treatment has caused considerable concern regarding the effects of occupational exposure on human health. Despite this concern, little information is available regarding possible effects and the mechanism behind chronic low-dose irradiation. The present study assessed potential genomic damage in workers occupationally exposed to low-dose X-rays. A variety of analyses were conducted, including assessing the level of DNA damage and chromosomal aberrations (CA) as well as cytokinesis-block micronucleus (CBMN) assay, gene expression profiling, and antioxidant level determination. Here, we report that the level of DNA damage, CA, and CBMN were all significantly increased. Moreover, the gene expression and antioxidant activities were changed in the peripheral blood of men exposed to low-dose X-rays. Collectively, our findings indicated a strong correlation between genomic instability and duration of low-dose IR exposure. Our data also revealed the DNA damage repair and antioxidative mechanisms which could result in the observed genomic instability in health-care workers exposed to chronic low-dose IR.