The Cellular and Molecular Carcinogenic Effects of Radon Exposure: A Review

Radon-222 is a naturally occurring radioactive gas that is responsible for approximately half of the human annual background radiation exposure globally. Chronic exposure to radon and its decay products is estimated to be the second leading cause of lung cancer behind smoking, and links to other forms of neoplasms have been postulated. Ionizing radiation emitted during the radioactive decay of radon and its progeny can induce a variety of cytogenetic effects that can be biologically damaging and result in an increased risk of carcinogenesis. Suggested effects produced as a result of alpha particle exposure from radon include mutations, chromosome aberrations, generation of reactive oxygen species, modification of the cell cycle, up or down regulation of cytokines and the increased production of proteins associated with cell-cycle regulation and carcinogenesis. A number of potential biomarkers of exposure, including translocations at codon 249 of TP53 in addition to HPRT mutations, have been suggested although, in conclusion, the evidence for such hotspots is insufficient. There is also substantial evidence of bystander effects, which may provide complications when calculating risk estimates as a result of exposure, particularly at low doses where cellular responses often appear to deviate from the linear, no-threshold hypothesis. At low doses, effects may also be dependent on cellular conditions as opposed to dose. The cellular and molecular carcinogenic effects of radon exposure have been observed to be both numerous and complex and the elevated chronic exposure of man may therefore pose a significant public health risk that may extend beyond the association with lung carcinogenesis.     

油茶肉质果和肉质叶开发价值及食用安全性分析

研究了油茶肉质果和肉质叶营养成分及食用安全性。成熟的肉质果（叶）各成分质量分数分别为：水分91．36％（91．58％）、蛋白质7．81％（6．56％）、脂肪3．7％（2．90％）、还原糖30．41％（21．83％）、总糖37．23％（29．28％）、茶皂素2．44％（1．46％）、灰分3．45％。（4．55％）、酸度0．35％（0．46％）。测定的矿物元素中，肉质叶、果的钙含量分别为411．3mg、359mg；锰的含量分别为31．35mg和33．06mg；含有16种氨基酸；所测的6种维生素中，维生素C和叶酸含量较高。毒性试验结果显示，样品为无毒野生果。微核试验和致畸试验结果表明：小鼠微核率与对照组比较，差异不显著（P〉0．05）。小鼠精子致畸率与阳性对照组比较无显著差异（P〉0．05）。样品对金黄色葡萄球菌抑制效果明显。该野生果基本无毒、无致突变物质，证明油茶肉质果、肉质叶是一种食用安全的野生果和食品资源。     

THE RELATION BETWEEN BIOMARKERS AND OCCUPATIONAL EXPOSURE TO POLYCYCLIC AROMATIC COMPOUNDS

Recently a paper was published in which we reviewed a number of studies involving occupational surveys, where both the external polycyclic aromatic hydrocarbon (PAH) exposures and one or more biomarkers were quantitatively monitored. As part of that review a statistical analysis of the results of these studies was performed, which revealed that only urinary 1-hydroxypyrene (1OHPy) and possibly chromosome aberrations (CA) showed a correlation with PAH exposure, while unexpectedly, DNA adducts did not. Another observation was that although in controlled laboratory experiments good correlations have been found to occur between DNA adducts and exposure doses to polycyclic aromatic compounds (PACs), such a correlation was not found in the human occupational exposure studies reviewed. Also the analyses showed that sister chromatid exchanges (SCE) and micronuclei (MN) exhibited a very weak or an absence of a correlation, respectively, with external PAH exposure. The subject of this article is an attempt to explain: (a) why the levels of only some biomarkers correlate with PAH exposures and (b) the differences in results between controlled animal experiments and human monitoring studies.     

鳖甲粗多糖预防辐射损伤效应的初步研究

研究了口服鳖甲粗多糖对受照射小鼠外周血白细胞数，巨噬细胞吞噬细功能以及外周血淋巴细胞微核的影响，结果表明，预防口服３ｄ鳖甲粗多糖，可明显升高受６ＧｙＸ照射小鼠的外周血白细胞总数，显著提高吞噬百分率，消化百分率及吞噬指数，并能降低外周血淋巴细胞微核率，提示：鳖甲粗多糖具有良好的减轻放射损伤作用，临床应用前景广阔。     

航天搭载对辣椒SP1代的诱变效应

为了研究航天搭载对辣椒的诱变效应,以3种卫星搭载当代(SP1)的辣椒种子为材料,对其根尖细胞进行了细胞遗传学分析.结果表明,与未搭载对照相比,航天诱变对辣椒SP1代种子根尖细胞的有丝分裂产生了促进效应,同时使根尖细胞产生了微核以及包括染色体桥、染色体断片、多极分裂等在内的多种类型的染色体变异,说明卫星搭载对辣椒根尖细胞具有诱变效应。     

A multiple technical approach to the study of apoptotic cell micronuclei

Apoptotic micronuclei have been studied, in different cell types, from a morphologic and functional point of view. Conventional electron microscopy, in various staining conditions, selective cytochemistry for DNA, and freeze fracture for the analysis of chromatin fiber organization and size were performed. In situ TdT and Pol I immunofluorescent techniques were carried out to detect double- and single-strand DNA breaking points by confocal laser scanning microscopy. Apoptotic cell ultrathin cryosections were also performed and were analysed by field emission in lens scanning electron microscopy. Double/single strand massively cleaved DNA was detected in micronuclei, with a highly supercoiled, uniformly packed, very dense arrangement.     

MTHFR Knockdown Assists Cell Defense against Folate Depletion Induced Chromosome Segregation and Uracil Misincorporation in DNA

Folate depletion causes chromosomal instability by increasing DNA strand breakage, uracil misincorporation, and defective repair. Folate mediated one-carbon metabolism has been suggested to play a key role in the carcinogenesis and progression of hepatocellular carcinoma (HCC) through influencing DNA integrity. Methylenetetrahydrofolate reductase (MTHFR) is the enzyme catalyzing the irreversible conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate that can control folate cofactor distributions and modulate the partitioning of intracellular one-carbon moieties. The association between MTHFR polymorphisms and HCC risk is inconsistent and remains controversial in populational studies. We aimed to establish an in vitro cell model of liver origin to elucidate the interactions between MTHFR function, folate status, and chromosome stability. In the present study, we (1) examined MTHFR expression in HCC patients; (2) established cell models of liver origin with stabilized inhibition of MTHFR using small hairpin RNA delivered by a lentiviral vector, and (3) investigated the impacts of reduced MTHFR and folate status on cell cycle, methyl group homeostasis, nucleotide biosynthesis, and DNA stability, all of which are pathways involved in DNA integrity and repair and are critical in human tumorigenesis. By analyzing the TCGA/GTEx datasets available within GEPIA2, we discovered that HCC cancer patients with higher MTHFR had a worse survival rate. The shRNA of MTHFR (shMTHFR) resulted in decreased MTHFR gene expression, MTHFR protein, and enzymatic activity in human hepatoma cell HepG2. shMTHFR tended to decrease intracellular S-adenosylmethionine (SAM) contents but folate depletion similarly decreased SAM in wildtype (WT), negative control (Neg), and shMTHFR cells, indicating that in cells of liver origin, shMTHFR does not exacerbate the methyl group supply in folate depletion. shMTHFR caused cell accumulations in the G2/M, and cell population in the G2/M was inversely correlated with MTHFR gene level (r = −0.81, p < 0.0001), MTHFR protein expression (r = −0.8; p = 0.01), and MTHFR enzyme activity (r = −0.842; p = 0.005). Folate depletion resulted in G2/M cell cycle arrest in WT and Neg but not in shMTHFR cells, indicating that shMTHFR does not exacerbate folate depletion-induced G2/M cell cycle arrest. In addition, shMTHFR promoted the expression and translocation of nuclei thymidine synthetic enzyme complex SHMT1/DHFR/TYMS and assisted folate-dependent de novo nucleotide biosynthesis under folate restriction. Finally, shMTHFR promoted nuclear MLH1/p53 expression under folate deficiency and further reduced micronuclei formation and DNA uracil misincorporation under folate deficiency. In conclusion, shMTHFR in HepG2 induces cell cycle arrest in G2/M that may promote nucleotide supply and assist cell defense against folate depletion-induced chromosome segregation and uracil misincorporation in the DNA. This study provided insight into the significant impact of MTHFR function on chromosome stability of hepatic tissues. Data from the present study may shed light on the potential regulatory mechanism by which MTHFR modulates the risk for hepatic malignancies.     

增敏化合物BSO对细胞微核率的影响

本文报道用微核胞质分裂阻断法研究BSO(丁胱亚磺亚酰胺,Buthione Sulfoximine)对细胞微核率的影响。研究结果表明BSO对正常人外周血淋巴细胞、BCa-P 37人乳腺癌细胞、中国仓鼠V79细胞和中国仓鼠CHO细胞在用药浓度0.1-2mmol/L情况下,微核发生率与未用药组无显著性差异,在~(60)COγ射线照射下,细胞的微核发生率与辐射剂量呈线性关系,当照射合并BSO时,微核发生率明显增加,表示BSO对细胞具有增加电离辐射的损伤作用。     

Is DNA Damage Response Ready for Action Anywhere?

Organisms are continuously exposed to DNA damaging agents, consequently, cells have developed an intricate system known as the DNA damage response (DDR) in order to detect and repair DNA lesions. This response has to be rapid and accurate in order to keep genome integrity. It has been observed that the condensation state of chromatin hinders a proper DDR. However, the condensation state of chromatin is not the only barrier to DDR. In this review, we have collected data regarding the presence of DDR factors on micronuclear DNA lesions that indicate that micronuclei are almost incapable of generating an effective DDR because of defects in their nuclear envelope. Finally, considering the recent observations about the reincorporation of micronuclei to the main bulk of chromosomes, we suggest that, under certain circumstances, micronuclei carrying DNA damage might be a source of chromosome instability.     

用蚕豆根尖微核实验分析水中铬的遗传毒性

用蚕豆根尖细胞微核实验对水中铬的遗传毒性和细胞毒性进行了检测分析。结果显示,将蚕豆根尖细胞暴露在铬质量浓度5 mg/L~100 mg/L的水中,细胞微核率明显增加,细胞有丝分裂指数明显下降。此外,细胞微核率与脂质过氧化反应之间有明显的相关关系,其相关系数R2=0.94。蚕豆根尖细胞微核实验监测水环境中铬的生态毒性具有简便、有效、重复性好的优点。