4-硝基酚对大鼠肝脏的毒性及氧化损伤

研究环境内分泌干扰物4-硝基酚(4-nitrophenol,PNP)对大鼠肝脏功能的毒性作用及其对核因子相关因子-2(Nrf2)通路的影响.20只SD雄性大鼠随机分成4个组,分别为对照组、1、10和100 mg·kg-1体重PNP处理组,连续皮下注射28d,检测肝脏的结构变化、氧化损伤和Nrf2及其相关基因的表达情况.结果表明,与对照组相比,100 mg·kg-1PNP处理组大鼠的血清肝功能主要指标ALT、AST、AKP活性和TBIL含量显著性升高p＜005);100 mg·kg-1组肝脏GSH-PX、CAT和SOD活性显著性降低p＜005);大鼠肝脏中Nrf2及其下游基因NQOI和HO-1 mRNA表达水平在1mg·kg-1组显著升高(p＜0.05),10、100 mg·kg-1组有升高趋势;100 mg ·kg-1组肝脏显微和超微结构都发现有不同程度的损伤.结果提示,皮下注射1 mg·kg-1 PNP引起了大鼠肝脏氧化损伤,机体可能通过提高Nrf2及其相关基因mRNA的表达水平来抵抗PNP引起的肝脏损伤;皮下注射100 mg·kg-1 PNP改变了肝脏的正常生理功能,造成肝细胞超微结构病理损伤,引起肝脏毒性.     

考虑损伤的圆形巷道围岩弹塑性分析

如何判断巷道开挖后,围岩弹塑性变形及围岩的力学行为一直是人们研究的重点问题。考虑岩石材料的损伤特性,建立了巷道围岩弹塑性损伤力学模型,对侧压力系数为1时圆形巷道围岩的弹塑性应力场及范围进行分析。结合具体算例,得出在相同塑性范围内,随着λ/E比值的增大,所需要的支护阻力也随之增大;当原岩应力一定时,随着λ/E比值的增大,巷道围岩的塑性区范围也随之增加。研究表明,考虑损伤作用使得分析结果更加接近于实际,从而为巷道围岩稳定性分析和合理选择支护形式及强度提供理论依据。     

Glutathione S-transferase gene polymorphism,cigarette smoking and DNA damage

Several factors such as smoking habits, diet, occupational, and environmental exposure to chemical carcinogens influence the overall level of DNA damage. In 69 healthy adult volunteers’ polymorphisms of glutathione S-transferase (GST), an enzyme which participates in the metabolism of a broad range of carcinogens and endogenous compounds were determined. The level of DNA damage was assessed by comet assay and classified according to GSTT1/M1 genotype and smoking habits. GSTM1 null genotype was recognized in 48% of studied subjects and GSTT1 null genotype in only two cases (3%). In subjects carrying GSTT1/M1 alleles a significantly lower degree of DNA damage, determined as % DNA in the comet's tail, than in null individuals was noted. However, the results obtained did not indicate that in studied subjects an elevated endogenous level of DNA damage may be significantly related to smoking habits.     

Mutagenic activity of transition‐metal complexes: Relation structure‐mutagenic and antibacterial activity for some Pd(II), Pt(II) and Rh(I) complexes†

The inhibitory and mutagenic action of some Pd(II), Pt(II) and Rh(I) complexes towards various bacterial strains has been evaluated, and some correlations have been found between the chemical behaviour of the complexes and their selective biological activity: most of the complexes cause only a DNA damage repaired by the excision repair system. Particularly, the Rh(I) complexes used in this work show selective antibacterial effects on defective but no effect on wild‐type strains.     

Chromosome damage in individuals exposed to heavy metals†

Testing the mutagenic activity of environmental pollutants has become an important area of modern environmental science and prophylactic medicine. The most suitable method for short‐term mutagenicity testing on man, at present, are chromosome studies on somatic cells of exposed individuals. Mutation types analyzed by such studies are of high practical relevance as indicator system of genetic damage induced in man under in vivo conditions. A rather large series of such studies has been dedicated to the action of heavy metals on individuals contacted with these metals under therapeutic, ecological or occupational conditions or by intoxication. Lead, cadmium, chromium, nickel, mercury, zinc and other metals as well as their compounds have been under study. Analyses of that kind, of course, are hampered by difficulties with the distinct estimation of the actual load as well as unclear conditions of exposition, e.g. simultaneous exposition to different metals.

Results obtained till now arouse some suspicion of a direct or indirect mutagenic activity in man by certain chromium and platinum compounds, arsenic, mercury, and combinations of lead with other heavy metals (cadmium, zinc, arsenic, antimony, etc.). Life style, above all smoking habits, well may act comutagenic. In most cases, however, mutagenic activity of metals and metal compounds apparently is clearly superposed by their toxic activity. In specific cases, chromosome studies also may contribute to discover sources of ecological exposition and to monitor occupational load by heavy metals.     

DNA damage in mouse organs and in human sperm cells by bisphenol A

Abstract

The in vivo genotoxic potential of bisphenol A using the comet assay in mice and in human sperm cells in vitro without metabolizing enzymes was studied. Male mice were exposed by oral gavage to the following doses of bisphenol A (0 125, 250 and 500?mg/kg body weight). DNA damage was investigated in liver, kidney, testes, urinary bladder, colon and lungs cells. In testicular cells, a significant increase in DNA strand breaks was observed in the lowest, but not in the medium or highest dose groups. Histopathological investigation of the testicular samples did not show any treatment dose-related effects. No DNA strand breaks were observed in any of the other investigated tissues. In human sperm cells in vitro, bisphenol A did not induce DNA strand breaks.     

生物样品体外致突变高通量检测方法研究进展

评述了几种常用的体外致突变检测方法及其用于生物样品检测的可行性,有些方法经改进可用于高通量检测生物样品体外致突变性.经典Ames实验受生物样品中组氨酸的影响,易产生假阳性结果,尽管经过修正可以排除组氨酸的干扰,但操作繁琐,不适合高通量检测.基于SOS反应的检测体系避开了组氨酸的影响,且简单易行,适合高通量检测:以β-半乳糖苷酶基因(lacZ)作为报告基因的检测体系灵敏度高,且经过离心洗涤或后培养的方式可降低样品颜色的影响;以绿色荧光蛋白(GFP)基因作为报告基因的检测体系避开了颜色的干扰,但这类方法灵敏度普遍不高,可以寻找信号更强的荧光蛋白以替代GFP;荧光素酶(lux)基因集lacZ和GFP的优点于一身,但检测时需要额外添加辅助因子,限制了其应用.也对单细胞凝胶电泳、tk基因突变实验、染色体损伤检测等方法进行了分析,有些适合生物样品高通量检测,但由于缺少国际通用的标准,很难推广使用.     

甲醛及苯系物混合暴露对小鼠肺脏的氧化损伤作用

为探讨甲醛、苯、甲苯及二甲苯混合气体急性暴露对小鼠肺脏的氧化损伤作用,选用雄性健康昆明种小鼠50只,随机分为对照组和4个染毒组。染毒组1到4中甲醛、苯、甲苯和二甲苯浓度依次为:1.0+1.1+2.0+2.0μg·L-1、3.0+3.3+6.0+6.0μg·L-1、5.0+5.5+10.0+10.0μg·L-1、10.0+11.0+20.0+20.0μg·L-1,各染毒组混合气体的浓度分别是我国室内空气质量标准(GB/T18883-2002)的10、30、50和100倍。用静式吸入染毒方式,每天染毒2h,共染毒10d,实验结束后,测定小鼠肺脏中的氧化损伤指标。结果表明:染毒组小鼠的体重增加幅度均低于对照组,肝脏和脾脏系数显著低于对照组,肺脏ROS、MDA含量随染毒剂量的增加而增加,T-AOC、GSH、CAT、GSH-Px及SOD活力随染毒剂量的增加而降低,并且ROS、MDA含量与混合气体的浓度呈显著的正相关关系,GSH含量与混合气体的浓度呈显著的负相关关系。研究结果显示,甲醛、苯、甲苯及二甲苯混合气体急性暴露对小鼠肺脏具有氧化损伤作用,混合气体的联合毒性效应强于单一组分,ROS、MDA和GSH可以作为评价VOCs急性暴露对机体氧化损伤作用的敏感生物学标志。     

双酚A对小鼠肝脏和肾脏细胞的氧化损伤

为探究双酚A(BPA)的氧化毒性,分别以剂量为20、40和80mg·kg~(-1)·d~(-1)的BPA对雄性昆明小鼠灌胃处理1周,并测定了小鼠体内活性氧自由基(ROS)水平、还原型谷胱甘肽(GSH)含量、丙二醛(MDA)含量和DNA-蛋白质交联系数(DPC)。与对照组相比,各BPA暴露组小鼠肝脏和肾脏细胞中的ROS生成量、MDA含量和DPC系数均升高,而GSH含量下降(P<0.05或P<0.01)。ROS生成量、GSH含量和DPC系数均显示出剂量-效应关系。研究表明,BPA可扰乱小鼠肝脏和肾脏细胞的氧化应激平衡,诱导细胞氧化损伤。