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Genotoxicity of 2-Amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) in Drosophila melanogaster and Enhancement of DNA Damaging Activity by Pretreatment with β-Naphthoflavone and Ethanol 2-氨基-1-甲基-6-苯咪唑[4,5 -b]吡啶(PhIP)对黑腹果蝇的遗传毒性及β-萘黄酮和乙醇预处理对DNA损伤活性的增强
Pub Date : 1998-02-28 DOI: 10.1248/JHS1956.44.34
T. Kasai, Takeshi Kitamura, Yukoh Takahashi, A. Mondo, T. Hirayama, Tetsushi Watanabe
The genotoxicity of 2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) was assayed by the wing spot test for detecting somatic cell mutations and the DNA-repair test for detecting DNA damage with Drosophila melanogaster. Although PhIP increased the frequency of small single spots in a dose-dependent manner in the wing spot test, no large single spots and twin spots were induced to a significant extent. In the DNA-repair test PhIP showed clear DNA-damaging activity. The DNA-damaging potency of PhIP was significantly increased when larvae were pretreated with β-naphthoflavone (BNF) 24-48 h after oviposition. Excessive reduction of the Rec- male/Rec+ female ratio was also observed in ethanol-pretreated stock compared with stock not pretreated. These results indicate that alcohol and BNF, both enzyme inducers, enhance the in vivo DNA-damaging activity of PhIP.
采用检测体细胞突变的翼斑试验和检测DNA损伤的DNA修复试验,研究了2-氨基-1-甲基-6-苯基咪唑[4,5 -b]吡啶(PhIP)对黑腹果蝇的遗传毒性。虽然PhIP在翼斑试验中以剂量依赖的方式增加了小单斑的出现频率,但未诱导出大单斑和双斑。在dna修复试验中,PhIP显示出明显的dna损伤活性。产卵后24 ~ 48 h,经β-萘黄酮(BNF)预处理后,PhIP的dna损伤力显著增强。与未预处理的鱼相比,经乙醇预处理的鱼的Rec-雄/Rec+雌比值明显降低。这些结果表明,乙醇和BNF都是酶诱导剂,可以增强PhIP的体内dna损伤活性。
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引用次数: 0
Remodeling of Vascular Endothelial Glycocalyx by Basic Fibroblast Growth Factor (Proceedings of the 23rd Symposium on Toxicology and Environmental Health) 碱性成纤维细胞生长因子重塑血管内皮糖萼(第23届毒理学与环境卫生学术研讨会论文集)
Pub Date : 1998-02-28 DOI: 10.1248/JHS1956.44.P30
T. Kaji, A. Miyamoto, S. Miyajima, C. Yamamoto, Y. Fujiwara, F. Koizumi
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引用次数: 0
Effect of P450-Inducers on the Hepatotoxicity of 2-Hexenal on the Leakage of Lactate Dehydrogenase from Primary Cultured Rat Hepatocytes p450诱导剂对2-己烯醛对原代培养大鼠肝细胞乳酸脱氢酶渗漏肝毒性的影响
Pub Date : 1997-12-31 DOI: 10.1248/JHS1956.43.331
T. Hirayama, A. Yoshikawa, T. Kasai, Tetsushi Watanabe, S. Ogawa
We have already reported the effect of several carbonyl compounds such as alkanals, 2-alkenals, glyoxals and malondialdehyde, which are formed from oxidized lipids, on the leakage of hepatic enzymes from primary cultured rat hepatocytes. In the case of 2-alkenals, the leakage of lactate dehydrogenase (LDH) took place in a dose-dependent manner and the hepatotoxicity was inhibited by the addition of ascorbic acid and glutathione. In this paper, we investigated the effects of P450-inducers on the hepatotoxicity of 2-hexenal, since the hepatotoxicity of 0.5 mM 2-hexenal against untreated hepatocytes was reduced to 36.7% and 46.3% by the addition of 10μM cimetidine and 1μM α-naphthoflavone, respectively. 3-Methylcholanthrene (MC), phenobarbital (PB), β-naphthoflavone (NF) and dexamethasone (DEX) were used as P450-inducers. In the treatment with 0.5 mM 2-hexenal, the LDH leakage of 3-MC induced hepatocytes was enhanced to 1.4-fold that of non-induced hepatocytes. In the 3-MC induced hepatocytes, the hepatotoxicity of 0.5 mM 2-hexenal was reduced to 38% with α-NF (0.1 μM). Therefore, it is suggested that 2-hexenal is metabolized to hepatotoxic substances by microsomal CYP 1A2 species.
我们已经报道了由氧化脂质形成的几种羰基化合物(如烷醛、2-烯醛、乙二醛和丙二醛)对原代培养大鼠肝细胞肝酶渗漏的影响。在2-烯醛的情况下,乳酸脱氢酶(LDH)的渗漏呈剂量依赖性,肝毒性通过添加抗坏血酸和谷胱甘肽来抑制。在本文中,我们研究了p450 -诱导剂对2-己烯醛肝毒性的影响,因为添加10μM西咪替丁和1μM α-萘黄酮后,0.5 mM 2-己烯醛对未处理肝细胞的肝毒性分别降低到36.7%和46.3%。3-甲基胆蒽(MC)、苯巴比妥(PB)、β-萘黄酮(NF)和地塞米松(DEX)作为p450诱导剂。在0.5 mM 2-己烯醛处理下,3-MC诱导肝细胞的LDH漏出量增加到非诱导肝细胞的1.4倍。在3-MC诱导的肝细胞中,α-NF (0.1 μM)可使0.5 mM 2-己烯醛的肝毒性降低至38%。因此,我们认为2-己烯醛是通过微粒体CYP 1A2代谢成肝毒性物质的。
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引用次数: 0
Antibacterial Characteristics of N-Alkyl-2-alkylthiopyridinium and N-Alkyl-4-alkylthiopyridinium Salts n -烷基-2-烷基硫代吡啶和n -烷基-4-烷基硫代吡啶盐的抗菌特性
Pub Date : 1997-10-31 DOI: 10.1248/JHS1956.43.251
K. Okazaki, T. Maeda, H. Nagamune, H. Kourai
N-Alkyl-2-alkylthiopyridinium (2TPX-n : X=I or Br, n=6-18) and N-alkyl-4-alkylthiopyridinium salts (4TPX-n), which have an electron-releasing group on the pyridine ring, were synthesized. Both 2TPBr-12 and 4TPBr-12 showed a wide and potent bactericidal spectrum of activity against Gram-negative bacteria (9 strains) and Gram-positive bacteria (3 strains), compared with N-dodecylpyridinium iodide (P-12) which has no substituents. The activity of these new compounds was not correlated with the hydrophobicity of the bacterial cell surface. This suggests that the bactericidal mechanism of 2TPBr-12 and 4TPBr-12 is different from that of P-12. The bactericidal and bacteriostatic activity of the new compounds against Escherichia coli K12 W3110 was closely influenced by their alkyl chain length. Since they have two hydrophobic alkyl chains in their structure, it seems that hydrophobic association between the molecule of 2TPX-n or 4TPX-n and medium components in the minimum inhibitory concentration measurement system caused the reduction in their apparent concentration. The bactericidal activity of these compounds was dependent on their bacterioclastic activity, and less dependent on their hydrophobicity (RM).
合成了吡啶环上有一个电子释放基团的n-烷基-2-烷基硫代吡啶(2TPX-n: X= 1或Br, n=6-18)和n-烷基-4-烷基硫代吡啶盐(4TPX-n)。与不含取代基的n -十二烷基碘化吡啶(P-12)相比,2TPBr-12和4TPBr-12对革兰氏阴性菌(9株)和革兰氏阳性菌(3株)均表现出广泛而有效的杀菌活性。这些新化合物的活性与细菌细胞表面的疏水性无关。这说明2TPBr-12和4TPBr-12的杀菌机制与P-12不同。新化合物对大肠杆菌K12 W3110的杀菌和抑菌活性与它们的烷基链长度密切相关。由于它们的结构中有两条疏水烷基链,因此在最小抑制浓度测量系统中,2TPX-n或4TPX-n分子与介质组分之间的疏水缔合可能导致它们的表观浓度降低。这些化合物的杀菌活性依赖于它们的抑菌活性,而不依赖于它们的疏水性(RM)。
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引用次数: 10
Recent Circumstances of Standards for Indoor Air Environment 室内空气环境标准近况
Pub Date : 1997-06-30 DOI: 10.1248/JHS1956.43.162
I. Ichikawa, T. Matsumura
Since the end of 1960s, with an increase in the economic growth, a large amount of chemical products made from fossil fuel have been used. In addition to the development and the modification of the products for building materials containing many kinds of hazardous chemicals, the techniques for the airtight construction of houses have been remarkably developed. In the latter half of 1970s, among people living in U.S.A. and northern Europe a new syndrome with headache, dizziness, and eye irritation, etc., which was later called as a sick building syndrome (SBS), has emerged. This syndrome was found to be caused by concentrated multiple pollutants such as volatile organic compounds (VOCs) and allergens from fungi and ticks in high airtight rooms with lower ventilation. Recently, the number of patients suffering from biological allergens and VOCs tends to increase. But in Japan the standard values we have in the law on the sanitary management for buildings are limited to those for such three materials as carbon dioxide (CO2), carbon monoxide (CO) and suspended particulate matter (SPM). Therefore, we describe in this report the necessity of the establishment of a new law on the indoor environmental standards for the prevention of our health against some kinds of indoor pollutants such as VOCs in cluding formaldehyde, nitrogen dioxide (NO2), ozone (O3) and asbestos produced not only in offices and working places but also in houses.
自20世纪60年代末以来,随着经济增长的加快,大量使用化石燃料制成的化工产品。除了对含有多种有害化学物质的建筑材料的产品进行开发和改造外,房屋的密闭性建筑技术也有了显著的发展。20世纪70年代后半期,在美国和北欧出现了一种新的症状,包括头痛、头晕、眼睛刺激等,后来被称为病态建筑综合征(SBS)。该综合征是由于在通风较差的密闭室内,挥发性有机化合物(VOCs)和真菌、蜱虫等过敏原等多种污染物浓度较高而引起的。近年来,生物过敏原和VOCs患者有增加的趋势。但在日本,建筑卫生管理法中规定的标准值仅限于二氧化碳(CO2)、一氧化碳(CO)和悬浮颗粒物(SPM)这三种物质。因此,我们在本报告中描述了建立新的室内环境标准法的必要性,以防止我们的健康免受一些室内污染物,如voc,包括甲醛,二氧化氮(NO2),臭氧(O3)和石棉,这些污染物不仅在办公室和工作场所产生,而且在家里产生。
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引用次数: 2
Improvement of Electrode of Tritium Enrichment Cell and Application to Tritium Monitoring in Environmental Surface Water at South Osaka Area 氚富集电池电极的改进及其在大阪南部地表水环境氚监测中的应用
Pub Date : 1997-04-30 DOI: 10.1248/JHS1956.43.114
Syojiro Kimura, A. Iwamoto, M. Inagaki
The experimental studies on the improvement of electrode materials used for the electrolytic enrichment of tritium and on the establishment of rapid procedure for the analysis of tritium and its application to tritium monitoring in environmental surface water at south Osaka area were carried out. The more efficient recovery rate and reappearance of tritium were obtained by the trial of the exchange of the electrode material from nickel (Ni) to iron (Fe) at high current condition. However, by considering the electrolytic corrosiveness of iron, a combined multi plate electrode of Fe (-)-Ni (+) (an effective surface area ; 63cm2) was adopted. In the case of such operational conditions that a current density ; 180 mA/cm2 and a cooling temperature ; 5°C using a 100 ml glass cell inserted into the electrode, time required for decreasing the volume of sample solution from 100 ml to 15 ml was more than 22 h. In addition the recovery rate and the concentration ratio of tritium were 90% and 6 times respectively. Then, the tritium activity of the water sample could be counted rapidly with a relative counting error of ±20% for 4 h in a low level liquid scintillation counter. By the trial using the above mentioned method for the tritium monitoring in environmental surface water at south Osaka area from 1986 to 1992, it was proved that the tritium activities decreased to the naturally producing level of tritium (BG) during this term and the decreasing half times of tritium concentration in this area by dilution were about 4 years.
对电解富集氚电极材料的改进、氚快速分析程序的建立及其在大阪南部地区环境地表水氚监测中的应用进行了实验研究。通过在大电流条件下将电极材料由镍(Ni)交换为铁(Fe)的试验,获得了更高的氚回收率和重现率。然而,考虑到铁的电解腐蚀性,Fe (-)- ni(+)组合多极板电极(有效表面积;采用63cm2)。在这样的操作条件下,电流密度;180 mA/cm2和冷却温度;在5°C下使用100 ml玻璃电池插入电极,将样品溶液的体积从100 ml减少到15 ml所需时间超过22 h。此外,氚的回收率和浓度比分别为90%和6倍。然后在低液位液体闪烁计数器中快速计数水样的氚活度,相对计数误差为±20%,持续4 h。1986 ~ 1992年对大阪南部地区环境地表水氚监测的试验证明,在此期间,该地区氚活度下降到氚的自然产生水平(BG),稀释后该地区氚浓度下降一半的时间约为4年。
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引用次数: 1
Intercalation of Six β-Carboline Derivatives into DNA 六种β-碳碱衍生物插入DNA
Pub Date : 1997-04-30 DOI: 10.1248/JHS1956.43.83
Z. Taira, Shingo Kanzawa, Chiemi Dohara, S. Ishida, M. Matsumoto, Y. Sakiya
The absorption spectra, ethidium bromide fluorescent spectra and circular dichroism (CD) spectra indicate that six β-carboline derivatives, norharman, harman, harmol, harmine, harmalol and harmaline intercalate into DNA. This result is supported by unwinding experiments using the superhelical plasmid pBR322 DNA, and the magnitude of intercalation except for harmalol decreased in the order of harmol>harmine>harmaline>harman>norharman. The potency of the interactions was further determined by spectrophotometric titration. The Scatchard plots were then analyzed using the Langmuir equation including two terms for specific and non-specific interactions. The interaction of the β-carboline derivatives with DNA is characterized as follows : 1) Substitution into the β-carboline skeleton rings decreases the number of binding sites. 2) The polar groups OH and OCH3 increase the binding affinity at the first specific term. 3) A decrease in the planarity of the β-carboline skeleton decreases the binding affinity. 4) The interaction of harmalol with DNA may be less potent than that of harmine.
吸收光谱、溴化乙啶荧光光谱和圆二色性(CD)光谱表明,6种β-卡波林衍生物诺哈曼、哈曼、哈摩、哈玛洛、哈玛洛和哈玛洛插入到DNA中。采用超螺旋质粒pBR322进行的解绕实验支持了这一结果,除harmalol外,插入量依次为harmol>harmine>harmaline>harman>norharman。用分光光度滴定法进一步测定了相互作用的效价。然后使用Langmuir方程对Scatchard图进行分析,其中包括特异性和非特异性相互作用的两项。β-碳碱衍生物与DNA的相互作用具有以下特点:1)取代到β-碳碱骨架环中减少了结合位点的数量。2)极性基团OH和OCH3增加了第一个特异项的结合亲和力。3) β-碳碱骨架平面度的降低降低了结合亲和力。4)哈玛洛尔与DNA的相互作用可能不如哈玛洛因强。
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引用次数: 59
Effects of Potassium Sorbate on the Decrease of Cellular GSH Levels in Cultured Rat Hepatocytes (Proceedings of the 22nd Symposium on Toxicology and Environmental Health) 山梨酸钾对培养大鼠肝细胞GSH水平降低的影响(第22届毒理学与环境卫生学术研讨会论文集)
Pub Date : 1997-02-28 DOI: 10.1248/JHS1956.43.P16
N. Sugihara, K. Furuno
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引用次数: 0
Possible Origin of Testicular Damage by Phthalic Acid Esters (Proceedings of the 22nd Symposium on Toxicology and Environmental Health) 邻苯二甲酸酯对睾丸损伤的可能来源(第22届毒理学与环境卫生研讨会论文集)
Pub Date : 1997-02-28 DOI: 10.1248/JHS1956.43.P21
M. Fukuoka, S. Niimi, Tetsu Kobayashi, Yu Zhou, T. Hayakawa
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引用次数: 8
Development of a Portable Cocaine-Selective Electrode (Proceedings of the 22nd Symposium on Toxicology and Environmental Health) 便携式可卡因选择电极的研制(第22届毒理学与环境卫生学术研讨会论文集)
Pub Date : 1997-02-28 DOI: 10.1248/JHS1956.43.P17
Kiyoyuki Watanabe, K. Okada, H. Oda, T. Katsu
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引用次数: 1
期刊
Japanese journal of toxicology and environmental health
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