互隔交链孢霉提取物诱发V_(79)细胞突变和NIH/3T3细胞转化作用的研究

本文报告首次用从食管癌高发区林县粮食中分离的互隔交链孢霉提取物261-B_2-3诱发体外培养的V_(79)细胞6-巯基鸟嘌呤耐受(TG~r)突变和NIH/3T3细胞形态转化获得成功。在实验组每毫升培养基中加入互隔交链孢霉提取物4、8、16和33微克可诱发V_(79)细胞突变,这一作用在有、无肝微粒体酶制作物激活的情况下,均获阳性。当互隔交链孢霉提物物浓度为每毫升培养基32、64和128微克时,可诱发NIH/3T3细胞产生相当高的克隆转化率,分别为35.47%、36.60%和43.14%。与对照组比有非常显著差异(p<0.01)。结果表明,该霉菌提取物中含有直接诱变物,并有可能含有致癌物。林县粮食中互隔交链孢霉的较重污染可能在该地区食管癌的发生中起一定作用。     

交链孢醇单甲醚诱发V79细胞突变的研究

交链孢醇单甲醚是从林县污染粮食中分离的互隔交链孢霉的提取物,经进一步纯化结晶获得,它是该霉菌的主要代谢产物之一。本文用V_(79)细胞突变的方法进行了交链孢醇单甲醚的致突变性研究。结果表明,在不加S-9和加S-9情况下,交链孢醇单甲醚均能诱发V_(79)细胞6-巯基鸟嘌呤抗性突变,随交链孢醇单甲醚剂量增大,突变频率增高,具有直线回归关系(P<0.01),但不加S-9时比加S-9时致突变作用更强,提示交链孢醇单甲醚是直接致突变物,可能与食管癌病因有一定关系。     

互隔交链孢霉提取物对细胞周期的影响

方法传代培养的人羊膜FL细胞进入对数生长期后,于无血清培养基中加入互隔交链孢霉提取物(简称261-B_2-3)处理,各组的终浓度分别为0、10~(-3)、10~(-2),10~(-1)mg/ml。在处理的第0、8、24和48小时各处理组各取一组细胞消化,制成单细胞悬液     

交链孢酚对体外培养的人胎儿食管上皮的作用

河南林县是我国食管癌高发区之一。流行病学调查证明,林县粮食中互隔交链孢霉的污染率高于低发区。该霉菌的乙醚、乙醇提取物均有明显的诱变性,将提取物进一步分离纯化,确定了数种有效成分,其中之一为交链孢酚(alternariol, AOH)。实验证明,     

互隔交链孢霉提取物261—B2—3在体外对DNA、RNA和蛋白质合成的影响

大多数化学致癌物均可影响DNA、RNA和蛋白质合成的过程。本文研究了从食管癌高发区林县粮食中分离出的互隔交链孢霉菌株261提取物261-B_2-3对这些大分子物质合成的影响。研究表明261-B_2-3对DNA和蛋白质的合成有明显的抑制,其作用强度呈明显的浓度相关性。但是它对RNA的合成无明显影响。三种大分子物质的合成对于261-B_2-3的敏感性顺序为:蛋白质>DNA>RNA。261-B_2-3对DNA和蛋白质抑制作用的类型和机理并不相同。在中止261-B_2-3的作用后,DNA的合成率持续下降,形成一谷值,属于模板损伤型,而蛋白质则呈递增型合成曲线,为干扰代谢型。261-B_2-3对大分子合成的干扰导致了细胞生物学和生化过程的紊乱,并有可能在诱变过程中起到一定作用。     

互隔交链孢霉提取物对淋巴细胞核仁形成区及细胞增殖周期的影响

本实验应用人类核仁形成区(NORs)选择性银染方法和细胞光度术,观察了互隔交链孢霉两菌株提取物261-B_2-3和C_(12)b_3-2对人淋巴细胞NORs活性的影响以及后者对细胞增殖周期移行的影响。结果显示,应用不同浓度的261-B_2-3和C_(12)b_3-2提取物处理细胞后,细胞携带Ag-NORs的染色体数明显减少,与对照组比较差异极显著(P<0.01)。表明两株提取物能明显抑制淋巴细胞NORs的活性。细胞暴露于不同浓度的C_(12)b_3-2提取物后,G_1%明显增多,S%和G_2+M%显著减少,与对照相比差异极显著(P<0.01)。说明C_(12)b_3-2提取物可能作用于G_1后期或S早期,延缓和阻滞了细胞周期的移行。     

食管癌患者对互隔交链孢霉诱变敏感性的研究

从河南林县粮食中分离出的互隔交链孢霉,经培养后提取物具有较强的致突变作用。经饲喂动物诱发出了前胃癌及乳头状瘤。但霉菌在食管癌发生中所起的作用,目前尚未明了,本研究的目的在于,应用霉菌提取物,诱发不同人群姐妹染色单体互换（SCE）,作为致癌剂最终生物效应指标,以探讨患者、患者家族成员以及低癌区正常健康人对霉菌提取物的敏感性,分析其霉菌在食管癌发生中所起的作用。     

用~32P后标记法研究交链孢酚及菜油油烟凝聚物对FL细胞DNA加成作用

交链孢酚是河南林县污染粮食中分离的互隔交链孢霉的代谢提取物，可能与食管癌的发病有关。菜油油烟凝聚物可能与非吸烟妇女的肺癌发生有关。人羊膜上皮细胞系ＦＬ细胞接触不同剂量的交链孢酚；及经β－萘磺酮诱导２４ｈ的ＦＬ细胞接触不同剂量的莱油油烟凝聚物，用~３２Ｐ后标记法检测其加成物，分别可分离到１个和４个主要加成物斑块，均有明显剂量依赖性关系，提示该两种物质有明显的细胞遗传毒效应。     

用^32P后标记法研究交链孢酚及菜油油烟凝聚物对FL细胞DN…

交链孢酚是河南林县污染粮食中分离的互隔交链孢霉的代谢提取物，可能与食管癌的发病有关，菜油油烟凝聚物可能与非吸烟妇女的肺癌发生有关。人羊膜上皮细胞系ＦＬ细胞接触不同剂量的交链孢酚；及经β－萘磺酮诱导２４ｈ的ＦＬ细胞接触不同剂量的菜油油烟凝聚物，用＾３２Ｐ后标记法检测其加成物，分别可分离到１个和４个主要加成物斑块，均有明显剂量依赖性关系，提示该两种物质有明显的细胞遗传毒效应。     

交链孢酚单甲醚对人淋巴细胞内环核苷酸水平的影响

淋巴细胞内环核苷酸水平的变化与免疫功能有关。交链孢酚单甲醚是食管癌高发区河南省林县粮食中分离中的主要污染菌互隔交链孢霉（亦称链格孢菌）的毒素之一，已有实验证实ＡＭＥ具有致突变性和致癌性。本实验从体外探讨了ＡＭＥ对人淋巴细胞内环核苷酸水平的影响。实验结果表明，ＡＭＥ能增高淋巴细胞内ｃＡＭＰ水平，不同浓度的ＡＭＥ在不同作用进点上，使细胞内ｃＡＭＰ含量比相应对照组升高１．５－２．０倍，并且在同一时点，随     

Development in in vitro toxicology

There are three principal pressures driving the development of in vitro toxicology: (1) the need for more efficient testing systems to cope with the large number of xenobiotics currently being developed; (2) public pressure to reduce animal experimentation; and (3) a need for a better understanding of the mechanisms of toxicity. Within this, in vitro toxicology is focused on local, systemic, and target-organ toxicity. It is becoming increasingly apparent that a step or decision-tree approach using input of a variety of experimental data (physicochemical properties, biokinetics, cytotoxicity) provides the most efficient system for predicting toxicity. Examples of the use of in vitro toxicity systems for prediction of systemic toxicity and target-organ (liver) toxicity are presented.Originally presented at ECCP 93.     

Age-related changes in polyamines in memory-associated brain structures in rats

Polyamines putrescine, spermidine and spermine are positively charged aliphatic amines and have important roles in maintaining normal cellular function, regulating neurotransmitter receptors and modulating learning and memory. Recent evidence suggests a role of putrescine in hippocampal neurogenesis, that is significantly impaired during aging. The present study measured the polyamine levels in memory-related brain structures in 24- (aged), 12- (middle-aged) and 4- (young) month-old rats using liquid chromatography/mass spectrometry and high performance liquid chromatography. In the hippocampus, the putrescine levels were significantly decreased in the CA1 and dentate gyrus, and increased in the CA2/3 with age. Significant age-related increases in the spermidine levels were found in the CA1 and CA2/3. There was no difference between groups in spermine in any sub-regions examined. In the parahippocampal region, increased putrescine level with age was observed in the entorhinal cortex, and age did not alter the spermidine levels. The spermine level was significantly decreased in the perirhinal cortex and increased in the postrhinal cortex with age. In the prefrontal cortex, there was age-related decrease in putrescine, and the spermidine and spermine levels were significantly increased with age. This study, for the first time, demonstrates age-related region-specific changes in polyamines in memory-associated structures, suggesting that polyamine system dysfunction may potentially contribute to aged-related impairments in hippocampal neurogenesis and learning and memory.     

休克过程中肾上腺髓质素变化的研究进展

Adrenomedullin (AM) is a new peptidergic regulator of vascular function. AM serves as a hormone, which has many biological properties, plays an important role in the many pathophysiological processes, especially shock. This review will highlight the structure, biological properties of AM and the relationship between AM and shock.     

Seasonal variations in acute toxoplasmosis in pregnant women in Slovenia

Between December 1999 and December 2004, 40 081 pregnant women were examined for toxoplasmosis with Toxo-IgG, Toxo-IgM enzyme immunoassay. Women with positive results were then retested with the Toxo-IgG avidity assay for recent toxoplasmosis. Recent acute toxoplasmosis in pregnant women was found to be significantly more frequent (p < 0.01) during winter than summer. The incidence of acute toxoplasmosis during winter-spring was also significantly more frequent (p < 0.025) than summer-autumn. This phenomenon should be taken into account when formulating preventive measures for toxoplasmosis, especially for pregnant women.     

Secular change in menarche in women in Madrid

The age at menarche was estimated by recollection in 1617 women between the ages of 18 and 60 in Madrid and a nearby suburb, Pinto. The population of Pinto is working-class and the Madrid group, taken from residential neighbourhoods , belongs to the upper middle class. In both groups we found a diminution in average age at menarche, from 14.04 to 13.02 years in Madrid and from 14.55 to 13.16 years from about 1935 to about 1965 in Pinto. These changes have been more intense in the group which is less well-off economically, where living conditions have varied much more drastically.     

Uteroglobin in the developing rabbit conceptus in vivo and in vitro

Summary Uteroglobin (UGL) was measured in day- 4 to day-10 rabbit conceptuses by a competitive ELISA. Levels in blastocyst fluid, tissues, coverings and in the early fetus were determined separately. The total amount of UGL increased from 18.4 ng to 6.8 g per conceptus. The UGL content of individual day-6 blastocysts was studied in vitro. Culturing was carried out up to 60 h in Ham's F10 medium with polyvinylpyrrolidone as macromolecular component, with and without progesterone, and with progesterone plus estradiol. UGL was determined in the blastocyst fluids, tissues with coverings and in the culture media. After labelling with [³⁵S]-methionine, protein patterns of total blastocysts and of culture media were analysed by two-dimensional gel electrophoresis and fluorography. The morphology of cultured blastocysts was examined by electron microscopy. During 60 h of culture, the blastocysts expanded in diameter by 84%, and released 19% of their initial UGL content into the medium, independent of the hormonal substitution. Neither de novo synthesis, nor degradation of UGL was found: the protein remained unlabelled in fluorography, and its total quantity was not significantly different from that of non-cultured controls. Trophoblast, endoderm and embryoblast cells showed well preserved cell organelles and intercellular junctions, while the morphological differentiation of the germ layer was inhibited.