Micronuclei in humans induced by exposure to low level of ionizing radiation: influence of polymorphisms in DNA repair genes

Understanding the risks deriving from protracted exposure to low doses of ionizing radiation has remarkable societal importance in view of the large number of work settings in which sources of IR are encountered. To address this question, we studied the frequency of micronuclei (MN), which is an indicator of DNA damage, in a population exposed to low levels of ionizing radiation and in matched controls. In both exposed population and controls, the possible influence of single nucleotide polymorphisms in XRCC1, XRCC3 and XPD genes on the frequency of micronuclei was also evaluated. We also considered the effects of confounding factors, like smoking status, age and gender. The results indicated that MN frequency was significantly higher in the exposed workers than in the controls [8.62+/-2.80 versus 6.86+/-2.65; P=0.019]. Radiological workers with variant alleles for XRCC1 or XRCC3 polymorphisms or wild-type alleles for XPD exon 23 or 10 polymorphisms showed a significantly higher MN frequency than controls with the same genotypes. Smoking status did not affect micronuclei frequency either in exposed workers or controls, while age was associated with increased MN frequency in the exposed only. In the combined population, gender but not age exerted an influence on the yield of MN, being higher in females than in males. Even though there is a limitation in this study due to the small number of subjects, these results suggest that even exposures to low level of ionizing radiation could have genotoxic effects and that XRCC3, XRCC1 and XPD polymorphisms might contribute to the increased genetic damage in susceptible individuals occupationally exposed to chronic low levels of ionizing radiation. For a clear conclusion on the induction of DNA damage caused by protracted exposure to low doses of ionizing radiation and the possible influence of genetic polymorphism in DNA repair genes larger studies are needed.     

Phosphorylation of cold shock domain/Y-box proteins by ERK2 and GSK3beta and repression of the human VEGF promoter

The hypoxia responsive region (HRR) of the VEGF promoter plays a key role in regulating VEGF expression. We found that the cold shock domain (Y-box) repressor proteins, dbpA and dbpB/YB-1, bind distinct strands of the human VEGF HRR. We find both dbpA and dbpB are phosphorylated by ERK2 and GSK3beta in vitro, and the binding of dbpB to single-strand VEGF HRR DNA is regulated by this phosphorylation. These findings suggest the ERK/MAPK and PI3K pathways may regulate VEGF expression in part through regulating the action of these repressor proteins.     

Effects of polymorphisms in nucleotide excision repair genes on glioma risk in a Chinese population

We performed a case-control study to assess the relationship between six single nucleotide polymorphisms (SNPs) of xeroderma pigmentosum complementation group F (XPF) on glioma risk in a Chinese population. The six SNPs were genotyped in 330 glioma cases and 652 cancer-free controls using a 384-well plate format on the Sequenom MassARRAY platform (Sequenom, San Diego, USA). Rs1800067 did not follow the Hardy–Weinberg equilibrium in the control group, and the genotype distributions differed significantly between the two groups for SNPs rs1800067 and rs2276466. For rs1800067, the variant genotype T/T was strongly associated with an increased risk of glioma when compared with the A/A genotype (OR = 3.77, 95% CI = 2.38–6.01). Individuals with the rs1800067 G allele had a relatively high risk of glioma in a dominant model (OR = 3.47, 95% CI = 2.26–5.37). The rs2276466 G/G genotype was significantly associated with a moderate increased risk of glioma (OR = 1.82, 95% CI = 1.10–3.02) in a codominant model, and variation of rs25489 was associated with a 1.31- and 1.78-fold glioma risk in dominant and recessive models, respectively. Our study is the first to identify polymorphisms in rs1800067 and rs2276466 as correlated with glioma susceptibility.     

重离子辐照酿酒酵母DNA损伤修复途径研究进展

重离子辐照通过直接和间接作用导致生物体DNA产生损伤,包括DNA的链断裂、碱基的插入或丢失以及氧化损伤等.DNA损伤直接影响复制、转录和蛋白质合成,同时还是突变的重要原因,因此,DNA损伤修复系统尤为重要.在酿酒酵母中,这些损伤主要是通过同源重组修复(homologous recombination repair,HRR)、碱基错配修复(mismatch repair,MMR)和碱基切除修复(base excision repair,BER)等途径来修复的.作为真核生物研究的模式生物,对于酿酒酵母DNA损伤修复的HRR、MMR和BER途径研究颇多,也不断有一些新的成果出现,特别是对于相关途径的完善和相关蛋白的深化更是研究热点,在此对近年来有关重离子辐照酿酒酵母DNA损伤修复途径方面的研究做一综述.     

Synergistic effect of TRM2/RNC1 and EXO1 in DNA double-strand break repair in Saccharomyces cerevisiae

In our recently published study, we provided in vitro as well as in vivo data demonstrating the involvement of TRM2/RNC1 in homologous recombination based repair (HRR) of DNA double strand breaks (DSBs), in support of such claims reported earlier. To further validate its role in DNA DSB processing, our present study revealed that the trm2 single mutant displays higher sensitivity to persistent induction of specific DSBs at the MAT locus by HO-endonuclease with higher sterility rate among the survivors compared to wild type (wt) or exo1 single mutants. Intriguingly, both sensitivity and sterility rate increased dramatically in trm2exo1 double mutants lacking both endo-exonucleases with a progressively increased sterility rate in trm2exo1 double mutants with short-induction periods, reaching a very high level of sterility with persistent DSB inductions. Mutation analysis of the mating type (MAT) locus among the sterile survivors with persistent HO-induction in trm2 and exo1 single mutants as well as in trm2exo1 double mutants revealed a similar small insertions and deletions events, characteristic of non-homologous end joining (NHEJ) that might have occurred due to the lack of proper processing function in these mutants. In addition, trm2ku80 and trm2rad52 double mutants also displayed significantly higher sterility with persistent DSB induction compared to ku80 and rad52 single mutants, respectively, exhibiting a mutation spectra that shifted from base substitution (in ku80 and rad52 single mutants) to small insertions and deletions in the double mutants (in trm2ku80 and trm2rad52 mutants). These data indicate a defective processing in absence of TRM2, with a synergistic effect of TRM2, and EXO1 in such processing.     

Effect of energy drink dose on exercise capacity,heart rate recovery and heart rate variability after high-intensity exercise

[Purpose]

The purpose of this research was to investigate the effects of exercise capacity, heart rate recovery and heart rate variability after high-intensity exercise on caffeine concentration of energy drink.

[Methods]

The volunteers for this study were 15 male university student. 15 subjects were taken basic physical examinations such as height, weight and BMI before the experiment. Primary tests were examined of VO₂max per weight of each subjects by graded exercise test using Bruce protocol. Each of five subject was divided 3 groups (CON, ECGⅠ, ECGⅡ) by matched method based on weight and VO₂max per weight what gained of primary test for minimize the differences of exercise capacity and ingestion of each groups. For the secondary tests, the groups of subjects were taken their materials before and after exercise as a blind test. After the ingestion, subjects were experimented on exercise test of VO₂max 80% by treadmill until the all-out. Heart rate was measured by 1minute interval, and respiratory variables were analyzed VO2, VE, VT, RR and so on by automatic respiratory analyzer. And exercise exhaustion time was determined by stopwatch. Moreover, HRV was measured after exercise and recovery 3 min.

[Results]

Among the intake groups, ECGⅡ was showed the longest of exercise exhaustion time more than CON group (p = .05). Result of heart rate during exercise according to intake groups, there was significant differences of each time (p < .001), however, not significant differences of each groups and group verse time (p > .05). Result of RPE during exercise according to intake groups, there was significant differences of each time (p < .001), however, not significant differences of each groups and group verse time (p > .05).

[Conclusion]

In conclusion, EDGⅡ showed the significant increase of exercise exhaustion time more than CON group (p=.05) and not significant differences in HR, RPE, RER, HRV, HRR, blood pressure (p > .05). Therefore, 2.5 mg/kg^-1 ingestion of energy drink might be positive effect to increase exercise performance capacity without side-effect in cardiovascular disease.