Absence of metallothionein 3 expression in breast cancer is a rare but favorable marker that is under epigenetic control

Cadmium (Cd²⁺), a known carcinogen, mimics the effects of estrogen in the uterus and mammary gland suggesting its possible involvement in the development and progression of breast cancer. This lab showed through analysis of a small set of archival human diagnostic specimens that the third isoform of the classic Cd²⁺ binding protein metallothionein (MT-3) is not expressed in normal breast tissue, but is expressed in some breast cancers and that expression tends to correlate with a poor disease outcome. The goals of this study were to verify that overexpression of MT-3 in a large set of archival human diagnostic specimens tends to correlate with poor disease outcome and define the mechanism of MT-3 gene regulation in the normal breast epithelial cell. The results showed that MT-3 was expressed in approximately 90% of all breast cancers and was absent in normal breast epithelium. The lack of MT-3 staining in some cancers correlated with a favorable patient outcome. High frequency of MT-3 staining was also found for in situ breast cancer suggesting that MT-3 might be an early biomarker for breast cancer. The study also demonstrated that the MCF-10A cell line, an immortalized, non-tumorigenic model of human breast epithelial cells, displayed no basal expression of MT-3, nor was it induced by Cd²⁺. Treatment of the MCF-10A cells with the demethylation agent, 5-aza-2′-deoxycytidine, or the histone deacetylase inhibitor, MS-275, restored MT-3 mRNA expression. It was also shown that the MT-3 metal regulatory elements are potentially active binders of protein factors following treatment with these inhibitors suggesting that MT-3 expression may be subject to epigenetic regulation.     

Indoor and outdoor air pollution and lung cancer in New Hampshire and Vermont

Indoor and outdoor air pollution is known to contribute to increased lung cancer incidence. This study is the first to address the contribution of home heating fuel and geographical course particulate matter (PM₁₀) concentrations to lung cancer rates in New Hampshire, USA. First, Pearson correlation analysis and geographically weighted regression were used to investigate spatial relationships between outdoor PM₁₀ and lung cancer rates. While the aforementioned analyses did not indicate a significant contribution of PM₁₀ to lung cancer in the state, there was a trend towards a significant association in the northern and southwestern regions of the state. Second, case-control data were used to estimate the contributions of indoor pollution and secondhand smoke to the risk of lung cancer with adjustment for confounders. Increased risk was found among those who used wood or coal to heat their homes for more than 10 winters before the age of 18, with a significant increase in risk per winter. Resulting data suggest that further investigation of the relationship between heating-related air pollution levels and lung cancer risk is needed.     

Pesticide in the Mississippi River floodplain and its possible linkage to colon cancer risk in the US

Result of this study shows that elevated colorectal cancer risk in Mississippi River floodplain of the United States is likely linked to historically high pesticide application. Mississippi River basin produces about 80% of major US crops and has about two-thirds of US pesticides used for agriculture. Historically, heavy pesticide application and agricultural irrigation were reported to result in high pesticide residues in surface water, fish and wells of Mississippi embayment. Risk ratio of colorectal cancer incidence in 86 counties of Mississippi River floodplain was about 29% higher than that of other counties in the 48 contiguous states. Risk ratio of colon cancer mortality in 63 counties of Mississippi embayment was 33% higher than that of other counties in the 48 states between 1999 and 2016. Risk ratios of colorectal cancer incidence and colon cancer mortality in Mississippi River floodplain are higher after smoking and diabetes factors were filtered off. Previous studies have linked exposure to pesticide with type-II diabetes and the latter was linked to increasing colon cancer risk by about 27%. Result here suggests that pesticide may be an independent risk factor directly associated with elevated colon cancer risk in Mississippi River floodplain.     

Speciation and carcinogenic classification—some limits of assessment and prevention procedures—the case of “nickel”

The speciation of nickel is of the highest importance for the definition of lists of substances for regulatory activity in terms of prevention, regarding possible cancer risk. A review is made of the different attitudes of outstanding administrations in front of nickel speciation. Some of them show a maximum of care in chemical definition, others reflect a lack of scientific rigor leading to generic classifications, more or less abusive. The great complexity of the chemistry and physicochemistry of nickel imposes the “two‐level speciation concept” (chemical and physicochemical), at least for compliance with the “Good Laboratory Practice” as far as experimental toxicology is concerned. Recommendations are exposed for the attention of toxicologists and regulators who have been for some years now extremely solicited for prevention aims.     

云南宣威地区燃煤排放颗粒物中石英矿物的特征

云南宣威地区是我国人群肺癌死亡率最高的地区之一,过往研究表明,该区的高肺癌死亡率可能与居民室内燃煤排放颗粒物中的多环芳烃(PAHs)有关,而最近研究发现,其中的nm级石英可能是导致肺癌发生的原因, 但鲜见该区燃煤排放颗粒物中细粒石英矿物的研究. 为探究燃煤排放细粒矿物的分布特征,采集了肺癌高发区宣威市来宾镇及周边5个乡镇煤矿中的15个煤样,使用光学显微镜、X射线衍射仪(XRD)、带能谱的扫描电镜(SEM/EDS)分析了煤样的煤岩组分及矿物组成. 结果表明:宣威煤以中挥发分、较高镜质组烟煤为主,煤中主要矿物为石英、鲕绿泥石、高岭石和方解石;不同煤样中,矿物质的结晶程度有所差异;单颗粒统计结果显示,在所统计的775个矿物颗粒中,石英颗粒占37.9%,并且粒径多分布在1~2μm之间; 石英矿物颗粒的形状不规则且以微粒的形式填充在煤缝隙中. 石英与鲕绿泥石共存的现象显示,宣威煤中石英来源于富含Fe和Al的硅质热液流,而非岩石碎屑沉积;此外,在肺癌高发区(来宾镇),其煤中Si+Fe质矿物颗粒含量较Si质矿物高. 今后将重点研究石英颗粒在Fe参与下的生物活性.      

云南宣威地区燃煤排放PM10的微观形貌和粒度特征

宣威地区肺癌发病率居全国首位,并且肺癌与室内燃煤关系密切. 为了解宣威地区室内燃煤排放PM₁₀的微观形貌和粒度特征,使用小流量Minivol采样器,分别于2011年1月、3月和12月对宣威地区6个代表性乡镇的18个农户及对照点——贵州六盘水幸福村2个农户室内、外的PM₁₀进行采样. 采用扫描电子显微镜分析样品的微观形貌,并对颗粒物粒度进行统计分析. 根据微观形貌特征将PM₁₀分为烟尘集合体(链状、蓬松状、密实状)、球形颗粒(燃煤飞灰和焦油球)、矿物颗粒(规则和不规则状)、生物颗粒及超细未知颗粒. 结果表明:宣威地区室内PM₁₀微观形貌差别较大;室、内外PM₁₀的粒度分布在0.1~0.4μm内的颗粒数量所占比例较大,而1μm以上颗粒体积所占比例较大;小粒径颗粒对颗粒物数量贡献较大,而少数大粒径颗粒对体积贡献较大;宣威地区和对照点室内的PM₁₀数量-粒度和体积-粒度分布相似,室外PM₁₀数量-粒度特征相似但体积-粒度分布有所差异. 宣威地区室内的烟尘集合体和球形颗粒分别占颗粒物总数的10.5%和23.6%,高于对照点 (分别为7.7%和11.3%).      

Reduced effect of Tasmanian devil facial tumor disease at the disease front

Pathogen-driven declines in animal populations are increasingly regarded as a major conservation issue. The Tasmanian devil (Sarcophilus harrisii) is threatened with extinction by devil facial tumor disease, a unique transmissible cancer. The disease is transmitted through direct transfer of tumor cells, which is possible because the genetic diversity of Tasmanian devils is low, particularly in the major histocompatibility complex genes of the immune system. The far northwest of Tasmania now holds the last remaining disease-free wild devil populations. The recent discovery of unique major histocompatibility complex genotypes in the northwestern region of Tasmania has raised the possibility that some animals may be resilient to the disease. We examined the differences in the epidemiology and population effects of devil facial tumor disease at 3 well-studied affected sites in eastern Tasmania and 1 in western Tasmania (West Pencil Pine). In contrast to the 3 eastern sites, there has been no rapid increase in disease prevalence or evidence of population decline at West Pencil Pine. Moreover, this is the only onsite at which the population age structure has remained unaltered 4 years after the first detection of disease. The most plausible explanations for the substantial differences in population effects and epidemiology of the disease between eastern and western sites are geographic differences in genotypes or phenotypes of devils and functional differences between tumor strains in the 2 regions. We suggest that conservation efforts focus on identifying whether either or both these explanations are correct and then, if resistance alleles exist, to attempt to spread the resistant alleles into affected populations. Such assisted selection has rarely been attempted for the management of wildlife diseases, but it may be widely applicable.     

云南宣威燃煤室内可吸入颗粒物质量浓度变化特征

应用中流量采样器TSP-PM10-PM2.5对我国肺癌高发区宣威地区6个乡村19家农户进行采样,运用滤膜称重法来分析不同燃料类型室内及相应室外的大气颗粒物质量浓度特征.结果显示,各村庄室内、室外PM10质量浓度比值(I/O)变化范围为1.74~2.87,说明室内PM10污染主要由室内污染源引起;做饭时段室内PM10污染比其他时段严重,尽管烟囱可以将大量的污染物排出室外,但室内颗粒物的质量浓度依然较高.室内PM10质量浓度依燃料类型从高到低依次为块煤用户>型煤用户>燃柴用户>用电用户,室内PM2.5质量浓度依燃料类型从高到低表现为块煤用户>燃柴用户>用电用户;块煤、型煤用户的室内PM10的质量浓度平均值(442.49μg/m3、399.14μg/m3)超过国家室内空气质量标准日均值150μg/m3,污染严重;燃柴和用电用户室内PM10的质量浓度平均值(145.50μg/m3、119.91μg/m3)低于国家室内空气质量标准日均值150μg/m3,污染较轻.块煤用户PM2.5质量浓度日均值(132.58μg/m3)超过2012年2月29日环境保护部发布的环境空气质量标准二级标准75μg/m3,而燃柴和用电户PM2.5的质量浓度(55.24μg/m3、65.02μg/m3)均低于环境空气质量标准二级标准75μg/m3,说明块煤用户室内细颗粒污染较重,用电和燃柴用户室内细颗粒物污染相对较轻.     

Epigenetic effect of long-term bisphenol A exposure on human breast adenocarcinoma cells

In this research, epigenetic effects of bisphenol A (BPA) on human breast cancer MCF-7 cells were analyzed. Genome-wide DNA methylation and gene expression were analyzed in MCF-7 cells exposed to BPA (10^?5 and 10^?6 mol/L for 5 weeks). No significant changes in the global level of 5-methyl-2′-deoxycytidine and 5-hydroxymethyl-2′-deoxycytidine were observed. DNA methylation profiling analysis indicated that BPA exposure resulted in the hypermethylation of FOXK2, LKB1, LMX1A and CUGBP2 and the hypomethylation of PTPRN2, TRIM27, BCAS3 and ZNF423. Decreased expression of apoptosis genes (P38 and BCL2L1) and increased expression of chemokine (Cxcl2 and ccl20) were detected. Changes of these genes were speculated to affect the ERα-related cell growth as well as cell apoptosis.     

Comparative Toxicity of PCBs and PBDEs Using Human Cancer Cell Lines and Zebrafish Embryos

研究了6种多氯联苯(PCBs)3,3′,4,4′-四氯联苯(PCB77)、2,3,3′,4,4′-五氯联苯(PCB105)、2,3′,4,4′,5-五氯联苯(PCB118)、3,3′,4,4′,5-五氯联苯(PCB126)、2,3,3',4,4',5-六氯联苯(PCB156)和商业型混合多氯联苯Aroclor1254,两种多溴联苯醚(PBDEs)2,2′,4,4′-四溴二苯醚(PBDE47)、十溴二苯醚(PBDE209)对人类癌细胞生长和斑马鱼脱膜与不脱膜胚胎发育的影响.8种化合物均使用0.01、0.1、1.0、10μmol·L-14个浓度进行1~6d的暴露实验.结果表明,PBDE209在最高浓度10μmol·L-1下对结肠癌细胞HCT116(暴露3d后)和RKO(暴露5d后)具有显著的生长抑制作用,所有化合物均对乳腺癌细胞没有显著影响.相比之下,化合物对受精后5~6h(5~6hpf)的斑马鱼胚胎的毒性效应显得比较明显,而各化合物对胚胎的致畸和致死效应又不相同,其毒性强弱依次为PCB126≈PCB156>PCB1254(Aroclor1254)>PBDE47>PCB77>PCB105≈PCB118≈PBDE209.其中PBDE209在未脱膜暴毒后均无致畸与致死现象,脱膜暴毒后最高浓度才表现出显著意义的致畸作用,而PBDE47在最高浓度下可产生高达80%的致畸率,这说明胚胎绒毛膜具有有效阻挡大分子物质如PBDE209进入的作用.PCBs的毒性效应与其空间结构密切相关.如PCB126和PCB105具有相同的分子式,前者在1μmol·L-1下就引起了显著的致死和致畸效应,而后者即使在10μmol·L-1下也没有显著的效应.实验结果也说明不同类型的实验对象所展示的毒性效应并不相同,化合物对体外培养的细胞和发育中的胚胎具有不同的影响.