6-azauridine triacetate induced hyper beta-alaninemia and its decrease by administration of pyridoxine

The effect of pyridoxine on 6-azauridine triacetate (6-AzUrd-TA) induced hyper beta-alaninemia was studied in New Zealand albino rabbits in three experiments. In each of the three experiments the animals were administered by gavage: Group 1 (Control), drinking water; Group 2, 6-AzUrd-TA; and Group 3, 6-AzUrD-TA with pyridoxine. While no beta-alanine was found in the control group or in pretreatment samples of the 6-AZUrd-TA and 6-AzUrd-TA + pyridoxine treated animals, high concentrations of this amino acid (191.0 +/- 91.6, 220.2 +/- 116.3, 103.2 +/- 64.4 nmol/ml) were found on the fourth and seventh days of 6-AzUrd-TA treatment with daily doses of 1.0 g/kg and 0.5 g/kg B.W. respectively. The drug induced hyper beta-alaninemia was significantly (p less than or equal to 0.05) reduced in all three experiments by simultaneous pyridoxine administration in daily doses of 50 mg/kg B. W. These results indicate, that daily repeated oral administration of 6-AzUrd-TA causes elevation of serum beta-alanine, which can be partially prevented by oral administration of pyridoxine. They also indirectly support the hypothesis, that 6-AzUrd-TA induced hyper beta-alaninemia is at least partially caused by the inhibition of beta-alanine degrading enzymes, that use pyridoxal phosphate as a coenzyme. Direct measurement of the enzyme activity is planned in our future studies.     

安阳市721例尘肺发病现状分析

尘肺病是一种严重危害接尘工人健康的职业病。了解和掌握尘肺病的发病情况 ,是当地卫生监督、监测部门的一项重要工作。现就安阳市 72 1例尘肺病人情况分析如下。1　资料来源全部尘肺病例均为河南省和安阳市尘肺诊断组诊断的病例资料。2　结果与分析截止 2 0 0 2年底 ,全市累计尘肺病发病共计 72 1例 ,安阳地区各种尘肺首次诊断期别分布情况见表 1。表 1　各种尘肺首次诊断期别尘肺种类ⅠⅡⅢ合计矽肺 2 81 1 4 1 30 6煤工尘肺 3781 1 389石墨尘肺 2 9 2 9石棉尘肺 4 4水泥尘肺 2 2电焊工尘肺 1 1合计 695 2 5 1 72 1表 1显示 ,尘肺种类中按…     

微囊藻毒素-LR的DNA损伤作用研究

目的探讨微囊藻毒素LR(MCLR)在不引起细胞毒性剂量情况下,能否引起细胞的DNA损伤,同时比较了MCLR对人肝细胞株(HL7702)和KB细胞(人口腔表皮癌细胞)的作用情况。方法利用四甲基偶氮唑盐微量酶反应比色(MTT)法测定细胞毒性,彗星试验检测细胞的DNA损伤。结果当MCLR在剂量为10～100μgL时,对这两种细胞活性无显著性影响,而HL7702细胞在30μgL时出现DNA损伤,且随着毒素剂量的增加,其DNA损伤更加明显。但在同等实验剂量下,未能见到KB细胞的DNA损伤。结论MCLR具有潜在的遗传毒性;且它导致的DNA损伤有具有胆汁酸转运系统的肝细胞系中表现出得更为显著。     

Testicular apoptosis and histopathological changes induced by a 2.45 GHz electromagnetic field

There is a growing public concern about the potential human health hazard caused by exposure to electromagnetic radiation (EMR). The objective of this study is to investigate the effects of 2450 mhz electromagnetic field on apoptosis and histopathological changes on rat testis tissue. Twelve-week-old male Wistar Albino rats were used in this study. Eighteen rats equally divided into three different groups which were named group I, II and III. Cage control (group I), sham control (group II) and 2.45 GHz EMR (group III) groups were formed. Group III were exposed to 2.45 GHz EMR, at 3.21 W/kg specific absorption rate for 60 minutes/ day for 28 days. There was no difference among the groups for the diameter of the seminiferous tubules, pyknotic, karyolectic and karyotic cells. However, the number of Leydig cells of testis tissue of the rats in group III was significantly reduced comparing with the group I (p < 0.05). Estimation of spermatogenesis using the Johnsen testicular biopsy score revealed that the difference between groups is statistically significant. The level of TNF-α, Caspase-3 and Bcl-2 were compared, and no significant difference was found between the groups. When Bax apoptosis genes and Caspase-8 apoptosis enzyme were compared, there were significant differences between the groups (p < 0.05). Electromagnetic field affects spermatogenesis and causes to apoptosis due to the heat and other stress-related events in testis tissue.     

微囊藻毒素-LR致HT17细胞毒性及DNA损伤

目的比较微囊藻毒素-LR(MCLR)对2种人肝癌细胞系HT17和HepG2的细胞毒性差异,研究MCLR对HT17细胞的氧化性DNA损伤作用。方法应用四甲基偶氮噻唑蓝法检测细胞毒性,免疫酶染色法检测细胞内8-羟基脱氧鸟嘌呤核苷(8-OHdG)水平。结果当剂量增加到1μg/ml时,MCLR对HT17细胞产生明显的细胞毒性,细胞存活率随着处理剂量的增加而降低。HT17细胞对MCLR的敏感性高于HepG2细胞。非毒性剂量的MCLR处理HT17细胞引起8-OHdG水平升高,处理剂量与8-OHdG水平之间呈现剂量-反应关系。结论HT17细胞对MCLR的毒性更敏感,可能与HT17细胞表达有机阴离子转运多肽(OATP)1B1有关。非毒性剂量的MCLR引起氧化性DNA损伤提示长期少量接触MCLR可能对人类健康产生潜在的远期危害。     

Retinal damage induced by red diode laser.

Widespread use of compact, low-cost diode lasers (pointers and illuminators) has ushered in an era where large numbers of the general public are accidentally or deliberately exposed to low-power laser radiation. The objectives of this study are both to determine the primate retinal lesion threshold for exposure to 650 nm diode laser radiation and to examine the risks of retinal damage from low-level (sub-threshold) ocular exposures. To this end, the ED50 and ED10 damage thresholds, their fiducial limits, and the slopes of the probability vs. dose curves have been examined in detail. In addition to conventional fundoscopy, exposed eyes were examined by confocal scanning laser ophthalmoscopy, fluorescein angiography, and histopathology at both the light and electron microscopic levels in attempts to discern tissue disruption following exposures below the ophthalmoscopic ED50 threshold dose. These alternative observation techniques did not identify detectable tissue disruption following exposures below the ophthalmoscopic lesion threshold dose.     

氯化铟对大鼠骨髓嗜多染红细胞微核的影响

目的研究氯化铟气管注入染毒对大鼠造成的遗传损伤和氧化损伤。方法选取32只雄性健康成年SPF级Wistar大鼠,随机分为4组[生理盐水对照组,低、中、高剂量(0.065、0.65和1.3 mg/kg)氯化铟染毒组],采用非暴露式气管内注入法染毒,HE染色法光镜下观察肺组织病理形态学变化,测定肺组织匀浆丙二醛(MDA)和超氧化物歧化酶(SOD)含量,对骨髓涂片进行嗜多染红细胞微核计数,并采用ICP-MS法检测大鼠全血和肺组织中铟的含量。结果 3个剂量组大鼠血铟、肺铟含量和骨髓嗜多染红细胞微核率均明显高于对照组(P0.01);中、高剂量组大鼠肺组织中MDA含量亦较对照组显著增加(P0.05),而SOD水平均显著低于对照组(P0.05);肺组织病理观察显示氯化铟染毒后大鼠气管周围充血明显,肺泡间隔、细支气管壁增厚,肺泡腔内充满细颗粒状蛋白样物质。结论氯化铟气管注入法染毒会引起大鼠血铟、肺铟蓄积,骨髓嗜多染红细胞微核率增加,发生氧化损伤和组织病理学改变。     

五氯酚钠诱导小鼠遗传损伤的研究

目的 观察不同剂量五氯酚钠(Na-PCP)在不同处理后引发小鼠体内免疫细胞的DNA链断裂损伤和微核形成作用。方法 采用单细胞凝胶电泳法(SCGE)分别测定ICR小鼠灌胃染毒0，25，50和100mg／ks后3和24h脾细胞、胸腺细胞和巨噬细胞的DNA链断裂损伤。同时观察了连续灌胃染毒1个月，剂量分别为0，6．25，12．5和25mg／kg时脾细胞DNA链断裂损伤情况；微核试验观察染毒24和48h骨髓嗜多染红细胞的微核形成。结果在不同剂量五氯酚钠染毒3h后，脾细胞出现DNA链断裂损伤的频率以及迁移距离在50和100mg／kg组明显高于对照；巨噬细胞在100mg／kg时出现明显的DNA损伤；但胸腺细胞在研究剂量范围内未见明显变化；染毒24和48h后，所有观察细胞均未出现明显的DNA链断裂损伤。五氯酚钠处理1个月未诱发脾细胞明显的DNA链断裂损伤。骨髓嗜多染红细胞微核在研究剂量范围内未明显增高。结论 100mg／kgNa-PCP可诱发小鼠体内脾脏细胞和巨噬细胞的DNA链断裂损伤，50mg／kgNa-PCP可诱导脾脏细胞DNA链断裂损伤，Na-PCP对胸腺细胞DNA损伤作用不明显：Na-PCP连续1个月作用未诱导脾细胞出现明显的DNA链断裂损伤。25～100mg／kgNa-PCP未诱导骨髓嗜多染红细胞微核增加。     

镍冶炼烟尘诱导哺乳动物细胞遗传物质损伤作用的研究

目的 研究2种镍冶炼烟尘致细胞毒性和DNA损伤的作用及其差异.方法 以某镍冶炼厂的镍冶炼炉前沉降尘和镍精炼车间沉降尘为受试物,用噻唑蓝(MTT)染色的方法 检测(受试物浓度分别为100.00、50.00、25.00、12.50、6.25、0.00μg/ml)作用6、12、18、24、36、48 h的细胞相对存活率;单细胞凝胶电泳技术检测(受试物浓度分别为100.0、50.0、25.0、12.5、0.0μg/ml))作用2、4、8 h其致细胞的DNA损伤.结果 随着染毒时间的延长和染毒剂量的增加,细胞存活率下降;2种冶炼烟尘引起的细胞拖尾率、尾矩和细胞尾部DNA含量增加.在浓度为100.00μg/ml的2种烟尘作用细胞48 h后,细胞的存活率仅为24.5%和26.5%;镍冶炼炉前沉降尘的各浓度组在不同时间诱导的细胞拖尾率和尾部DNA含量均高于阴性对照组,差异有统计学意义(P<0.05),镍精炼车间沉降尘除12.5μg/ml各作用时间组和50.0μg/ml作用2 h组外的各实验组在不同时间诱导的细胞拖尾率和尾部DNA含量均高于阴性对照组,差异有统计学意义(P<0.05).结论 镍冶炼烟尘可以降低细胞的相对存活率,并不同程度地致NIH/3T3细胞的DNA损伤.     

Testicular atrophy of mice induced by ethylene glycol mono alkyl ethers (author's transl)]

Toxicities of ethylene glycol (EG) and 6 ethylene glycol mono alkyl ethers administered orally were studied. Mice were given various doses (62.5, 125, 250, 500, 1,000, 2,000 and 4,000 mg/kg body weight) of the compounds daily for 5 days/week, for 5 weeks. High doses of ethylene glycol mono methyl ether (EGM), ethylene glycol mono methyl ether acetate (EGMA), ethylene glycol mono ethyl ether (EGE) and ethylene glycol mono ethyl acetate (EGEA) produced marked testicular atrophy and leucopenia. Dose-responce relation was found in these effects. EGM was more effective than EGE, while ethylene glycol mono butyl ether and ethylene glycol mono phenyl ether had but slight effect and EG had no detectable action on testis and leucocytes. Toxic doses being expressed as mg/kg body weight, esterification seemed to weaken the atrophic action of EGM and EGE, but when expressed as mol/kg, significant difference was found neither between EGM and EGMA nor between EGE and EGEA. The mechanism of testicular atrophy induced by low ethylene glycol mono alkyl ethers is likely to be an inhibitory action on cell division.     

Genetic damage induced by occupationally low mercury exposure.

Lymphocytes from whole blood cultures from 28 subjects occupationally exposed to different mercury compounds and from seven control subjects were studied cytogenetically. Differences between aneuploidy of exposed and nonexposed subjects were found statistically significant for all analysed mercury compounds. No statistically significant difference however (except for ethylmercury exposure) was observed for the frequency of cells with structural chromosome aberrations although all of the observed frequencies in exposed subjects were higher than those of the controls. A significant correlation was found between the blood and urine mercury levels on the one hand and the total amount of cells with chromosomal aberrations and frequencies of cells with other than chromatid type aberrations on the other.     

Corneal damage induced by pulsed CO2 laser radiation

Corneal damage thresholds were determined in Dutch Belted rabbits following CO2 laser radiation with pulse widths of 1.7, 25 and 250 ns. The threshold values for corneal clouding found for the 3 cases were 0.33, 0.54 and 0.18 J/cm2, respectively. These results are in accord with expectations based on a thermal-damage mechanism, with no evidence of acoustic shock or other mechanisms contributing to the observed damage for the exposure parameters used in this study. The data support the suggested maximum permissible exposure levels for short-pulse far-infrared laser radiation as quoted in current laser safety standards.     

急性镉染毒对大鼠肾脏线粒体的损伤

目的 研究急性镉染毒对大鼠肾脏线粒体形态和功能的影响.方法 健康成年雄性SD大鼠随机分为4组,每组6只.分别给予大鼠皮下注射染镉0.6、1.2、1.8 mg/kg(CdCl2),对照组注射相应容积生理盐水,每天1次,连续注射5 d.用透射电子显微镜观察肾脏线粒体超微结构变化,差速离心法制备大鼠肾脏线粒体,Clark氧电极法测定线粒体呼吸功能,荧光法测定线粒体膜电位,分光光度法测定线粒体肿胀,四唑盐(NBT)法测定线粒体超氧化物含量.结果 电子显微镜观察显示,镉染毒对大鼠肾脏线粒体的损伤明显,表现为线粒体基质空泡增多、线粒体肿胀色泽加深.随染毒剂量的增加,大鼠肾脏线粒体损伤加重.与对照组相比,高剂量组线粒体Ⅲ态呼吸速率(V3)[(6.25±0.61)nmol/L O2·min-·mg-1]明显低于对照组[(9.66±1.16)nmol/L O2·min-·mg-1],RCR值(2.453±0.23)亦明显降低,差异均有统计学意义(P＜0.01,P＜0.05),提示线粒体呼吸功能受阻;线粒体膜电位水平(85.89%±3.82%)明显低于对照组(100.00%±3.43%),差异有统计学意义(P＜0.05),而氧自由基水平(116.33%±3.06%)则较对照组(100.00%±2.25%)明显上升,差异亦有统计学意义(P＜0.05).结论 急性镉染毒可造成大鼠肾脏线粒体损伤,引起线粒体呼吸功能受阻,膜电位降低,肿胀程度加剧,而这些损伤效应可能与线粒体内氧自由基水平增加有关.     

顺铂致小鼠肾损伤超微结构变化

目的：研究顺铂（DDP）所致肾毒性作用。方法：小鼠随机分为3组，阴性对照组、DDP组、分别给药处理后，取肾脏做病理组织学的光镜和电镜检查。结果：病理结果显示顺铂造成了小鼠肾结构的改变，主要表现为肾曲管上皮细胞浊肿，电镜结果显示，对照组呈现正常结构，DDP组曲管上皮细胞线粒体严重空泡化，嵴断裂；刷状缘微绒毛融合、破坏；基底皱纹消失；肾小球结构的足突部分融合，基底膜增厚走向紊乱，内皮细胞肿胀，模糊不清，间质纤维化，本次实验还发现顺铂可以使曲管内皮细胞水肿、模糊不清、此损伤国内未见报道。     

二氯乙烯对体外培养人皮肤角质形成细胞的氧化损伤作用

目的探讨二氯乙烯(dichloroethylene,DCE)对体外培养的人皮肤角质形成细胞(keratinocyte,KC)的氧化损伤作用。方法使用2.800、1.400、0.700、0.350、0.175 mmol/L的DCE对体外培养的人KC染毒4 h,检测细胞活力和细胞内MDA、ROS含量、SOD活性,以及线粒体内8-羟基脱氧鸟嘌呤(8-hydroxy-2-deoxyguanosine,8-OHdG)水平。结果经不同浓度DCE作用4 h后,细胞活力无明显改变。随着DCE浓度升高,细胞内MDA和ROS水平呈上升趋势,而SOD活性呈下降趋势,与溶剂对照组相比较差异有统计学意义;线粒体内8-OHdG水平也随着DCE浓度增加而呈现上升趋势。结论 DCE对人KC有氧化损伤作用。     

镉致DNA损伤及对原癌基因蛋白表达的影响

目的 研究氯化镉致人细胞和整体动物DNA损伤作用和对原癌基因等相关蛋白表达的影响.方法 雄性Wistar大鼠,体重约150 g,按每组8只分为1个对照组和2个染毒剂量组,以生理盐水配制氯化镉溶液经皮下注射进行染毒,剂量分别为5和20 μmol/kg,对照组注射生理盐水.用集落形成实验和四唑盐比色法（MTT）测定氯化镉的细胞毒性,用彗星实验检测氯化镉对DNA的损伤,采用流式细胞术测定细胞周期的变化,用免疫印迹和X-Gal染色检测相关蛋白的表达改变.结果 镉能明显抑制细胞增殖,对人成纤维和整体动物细胞DNA有明显的损伤作用,成纤维细胞彗星细胞率由对照组的6.1%增加到200μM剂量组的23.2%,差异有统计学意义（P＜0.01）.雄性大鼠各个脏器在镉染毒后彗星细胞的频率均随剂量的增高而增加,其中肾和腹侧前列腺的DNA损伤同对照组比较差异有统计学意义（P＜0.05）,镉能进一步引起细胞周期阻滞.原癌基因c-myc、c-Jun和老化标记蛋白β-Gal均被氯化镉诱导增加.结论 氯化镉能致DNA损伤并进一步引起细胞周期停滞,导致细胞老化、死亡.氯化镉诱导细胞的DNA损伤和原癌基因表达的增加也可能是镉致癌的重要原因.     

氧化乐果对小鼠睾丸Sertoli细胞DNA的损伤作用

目的 研究有机磷农药氧化乐果对小鼠睾丸Sertoli细胞DNA的损伤作用.方法 将40只清洁级昆明雄性小鼠随机分为对照(蒸馏水)组和1.0、2.0、4.0 mg/kg氧化乐果染毒组,每组10只.采用灌胃方式进行染毒,染毒容量为20 ml/kg,每天1次,连续染毒14d.采用单细胞凝胶电泳技术检测小鼠睾丸Sertoli细胞的DNA损伤情况.结果 与对照组比较,2.0、4.0 mg/kg氧化乐果染毒组彗星长度均明显增加,各剂量氧化乐果染毒组彗星尾长、Olive尾矩、尾长/头长、尾部DNA含量也均升高,差异有统计学意义(P＜0.05).且随着氧化乐果染毒剂量的升高,各指标均呈上升趋势.结论 氧化乐果对小鼠睾丸Sertoli细胞DNA有明显的损伤作用.     

黄磷中毒性肝损害的机理探讨

本研究表明,肝微粒体混合功能氧化酶参与了黄磷在体内的活化代谢,促进了肝毒作用。肝谷胱甘肽及其酶系参与了黄磷的解毒代谢,当其耗损或失代偿时,可为脂质过氧化或钙泵障碍提供发生条件,所得数据较充分证明:脂质过氧化是黄磷中毒性肝损害十分重要的机理,但不能认为是唯一的机理,它与钙泵障碍的相互关系,值得进一步研究。电镜及组化的研究发现,线粒体和粗面内质网是黄磷的靶细胞器,其功能和结构改变,是各种病理改变的基础。