Studies on the role of moderate doses of ionizing radiation-induced cellular senescence in mouse lung tissue.

PURPOSE: To investigate the role of moderate doses of ionizing radiation-induced cellular senescence in mouse lung tissue and whole-body inflammation levels. MATERIAL AND METHODS: Forty-two C57BL/6J mice were randomly divided into the control group, the 1, 3, and 7 days after 2 Gy irradiation group, and the 1, 3, and 7 days after 4 Gy irradiation group, with six mice in each group. The histopathology, cellular senescence, oxidative-antioxidant, DNA damage repair, and inflammation-related indicators of irradiated mice were examined. RESULTS: Compared with the control group, the histopathological scores, the positive area of senescence-associated-ß-galactosidase (SA-ß-Gal) staining, and the mRNA levels of senescence-related genes in the lung tissues in all dose groups increased on 1, 3, and 7 days after irradiation. In peripheral blood, erythrocytes, leukocytes, platelets, hemoglobin, 8-hydroxydeoxyguanosine (8-OHdG), C-reactive protein, and other indicators showed a different trend in all dose groups. The levels of malondialdehyde(MDA), superoxide dismutase (SOD), glutathione (GSH), and 8-OHdG in the lung tissue showed different trends after 2 Gy and 4 Gy irradiation. The 8-Oxoguanine DNA glycosylase 1 (hOGG1) and O-6-methylguanine-DNA methyltransferase (MGMT) mRNA levels showed a trend of increasing and then decreasing. The levels of whole-body inflammation were significantly correlated with the levels of indicators related to cellular senescence and damage repair in the lung tissue of mice. CONCLUSIONS: The moderate doses of ionizing radiation induce oxidative stress, and DNA damage and increase DNA repair gene expression in mouse lung tissue. The lung tissue cellular senescence correlates with the level of whole-body inflammation.

Functional analysis of polymorphism haplotypes of MGMT in residents of high background radiation area.

To investigate the distribution of polymorphisms and their frequent haplotypes in the regulatory region of MGMT in residents of high background radiation area (HBRA) and their impacts on transcriptional activity, we collected DNA samples from 83 healthy Chinese residents in HBRA and searched for genetic polymorphisms in the regulatory region of MGMT. Haplotypes were characterized by Haploview analysis. Transcriptional activities of different polymorphism haplotypes were detected by using a dual-luciferase reporter assay. Six genetic polymorphisms were identified within the regulatory region (1024 bp) of MGMT. Linkage disequilibrium (LD) patterns and haplotype profiles were analyzed using the identified genetic polymorphisms. These polymorphisms we found to be in high LD, with a D' of 0.928 (r2 = 0.581) for -808 T>C and -19 C>T, 0.928 (r2 = 0.581) for -797 G>A and -19 C>T in Han Chinese HBRA residents. Complete LD with a D' of 1.0 (r2 = 1.0) was observed between -808 T>C and -797 G>A. Haploview analysis revealed the existence of three polymorphism haplotypes in the core region of regulatory region of MGMT. Using serially truncated regulatory region of human MGMT luciferase reporter gene constructs, we found a 1002 bp (-637 nt to +365 nt) fragment in the MGMT gene was the core region. Dual-luciferase reporter assays showed that different polymorphism haplotypes bearing different variant alleles exhibit distinct transcriptional activities, especially the polymorphism haplotype carrying -19 T has the strongest transcriptional activity. In summary, the present study obtained genetic characteristics of the six polymorphisms in the regulatory region of the MGMT gene in HBRA residents, and the results suggest that different polymorphism haplotypes have significant effects on the transcriptional activity of the MGMT and that the -19 C>T polymorphism may be a functional variant involved in the transcriptional regulation of the MGMT gene.

Analysis of occupational stress and its correlation with oxidative-antioxidant levels among employees of a power grid enterprise in Guangdong.

BACKGROUND: Occupational stress and its health effects on occupational populations have attracted extensive attention from researchers in public health. The stressors faced by employees of power grid enterprises are increasing progressively, which is easy to cause occupational stress. The balance of the body's oxidative-antioxidant levels plays an essential role in maintaining the body's health status. This study aims to explore occupational stress and its correlation with oxidative-antioxidant levels in employees of a power grid enterprise. METHODS: A cluster random sampling method was used to investigate the basic information of 528 employees in a power grid enterprise and investigate the two occupational stress models of employees by using the Job Content Questionnaire based on the job demand-control-support (JDC) model, and the Effort-Reward Imbalance Questionnaire based on the effort-reward imbalance (ERI) model, respectively. Peripheral blood samples were collected from the employees to measure the levels of malondialdehyde (MDA), total antioxidant capacity (TAC), and superoxide dismutase (SOD). The correlation between different models of occupational stress level and the body's oxidation-antioxidation level was further explored. RESULTS: The detection rate of high JDC model occupational stress was 50.6% and the detection rate of high ERI model occupational stress was 50.9%. The JDC model occupational stress was significantly associated with high-temperature and high-altitude operation, visual display terminal operation, monthly income, and exercise (all P < 0.05). The ERI model occupational stress was significantly associated with visual display terminal operation (all P < 0.05). The results of the generalized additive model showed that SOD levels had a non-linear relationship with the D/C ratio as well as the E/R ratio. With the D/C ratio close to 1, SOD levels raised rapidly. When the E/R ratio exceeded 1, the SOD level raised rapidly (all P<0.05) . TAC levels were negatively associated with the E/R ratio (P < 0.05). CONCLUSION: The detection rates of occupational stress in both models among employees in a power grid enterprise are higher. ERI model occupational stress was associated with body TAC and SOD levels, and JDC model occupational stress was associated with body SOD levels.