Comparative studies on cytotoxic and genotoxic effects of two organic mercury compounds in lymphocytes and gastric mucosa cells of sprague-dawley rats

Human lymphocytes (HL) as well as lymphocytes (RL), hepatocytes (RH), and gastric mucosa cells (GM) of Sprague-Dawley rats were treated in vitro for 1 h with methylmercury chloride (MMC, 0.5–4 μg/ml) and dimethylmercury (DMM, 5–40 μg/ml). The cytotoxicity of the two organic mercury compounds was assessed by dye exclusion, and the extent of induced DNA fragmentation was measured with a single-cell microgel electrophoresis assay. Both MMC and DMM induced DNA damage and cytotoxicity in a dose-related manner in HL, RL, and GM. MMC was more effective in causing a significant increase in median DNA migration than DMM at doses yielding approximately the same degree of cytotoxicity. In rat hepatocytes the MMC-induced DNA damage was, however, lower than in the other cells. An analysis of repair kinetics following exposure to 2 μg/ml MMC was carried out in human lymphocytes obtained from an adult male donor. The bulk of DNA repair occurred 90 min after in vitro exposure, and it was about complete by 120 min following cessation of exposure. Finally, in order to have a basis for extrapolating to the human situation, in vivo studies were performed with Sprague-Dawley rats, also assessing the DNA damage and cytotoxicity in the lymphocytes and gastric mucosa cells. These in vivo results after oral exposure may be directly compared to the in vitro data obtained in the same cells. © 1993 Wiley-Liss, Inc.     

Light‐Switchable Supramolecular Self‐Assembly of Soft Colloids

Self‐assembly is an efficient strategy of constructing microgel‐based intelligent materials. However, it remains a challenge to realize the reversible self‐assembly of microgels. Herein, a method to guide the self‐assembly of soft colloids with light‐stimuli is proposed, utilizing the light‐responsive host–guest interaction between an azobenzene functionalized nanogel (the guest colloid) and an α‐cyclodextrin functionalized microgel (the host colloid). The two colloids can form a stable colloid cluster when the surface of the host colloid is fully packed with the guest colloids. The colloid cluster can disassemble when irradiated with UV light and reassemble when irradiated with visible light. The reversible colloidal self‐assembly can be controlled by the interplay between the supramolecular and covalent crosslinking, and can also be adjusted by the addition of competitive host molecules. Besides the light‐sensitivity, the colloid cluster inherits the deformability and temperature‐sensitivity from its parent colloids. These features are different from the supramolecular self‐assembly of hard colloids or macroscopic gels, and manifest the as‐prepared colloid cluster potential building blocks of light‐responsive materials.     

四乙基铅对小鼠脑细胞DNA的损伤作用

目的:了解四乙基铅对小鼠脑细胞DNA的损伤作用。方法:用单细胞凝胶电泳技术研究脑细胞DNA的损伤。结果:在染毒条件下,7~28mg/m3浓度的四乙基铅均可引起小鼠脑细胞DNA的损伤,且随四乙基铅浓度的增高,DNA损伤加重,具有明确的剂量效应关系。结论:四乙基铅能引起小鼠脑细胞DNA突变,呈剂量效应关系。     

相转变温度范围窄的聚(N-异丙基丙烯酰胺)温敏性微凝胶

采用间歇式、半间歇式和连续式无皂乳液聚合(SFEP)法合成温敏性聚(N-异丙基丙烯酰胺)(PNIPAM)微凝胶。连续式或半间歇式SFEP法合成的PNIPAM微凝胶相转变温度范围明显地比间歇式SFEP法合成的窄,其中又以连续式SFEP法的效果最明显。相同交联剂用量的情况下,连续式SFEP法合成的PNIPAM微凝胶的粒径和溶胀比最大,而间歇式SFEP法合成的最小。通过研究微凝胶合成过程中溶胀比随反应时间的变化关系,证明了连续式或半间歇式SFEP法合成的PNIPAM微凝胶具有比较均匀的内部交联结构。     

DNA double-strand breaks in mouse kidney cells with age

A Biojector device fitted with a CO₂ cartridge was used to prepare single cellsuspensions from kidneys of 12-month-(middle-aged) and 24-month-old (old) C57Bl/6mice. Microgel electrophoresis of DNA fromthese cells revealed a modest but significant7.3% increase (P = 0.04) in DNA double-strand breaks in old mice. This increase is equivalent to the DNA damage induced by 0.1 Gray of X-rays (5 double-strand breaks) in kidney cells of 10-month-old mice, as determined by a standard calibration curve. Greater DNA damage with aging was also positively correlated with higher levels of pathology in the kidneys.     

Detection of genotoxic effects in human gastric and nasal mucosa cells isolated from biopsy samples

To assess genotoxic burdens from chemicals, it is necessary to relate observations in experimental animals to humans. The success of this extrapolation would be increased by including data on chemical activities in human tissues. Therefore, we have developed techniques to assess DNA damage in human gastric and nasal mucosa (GM, NM) cells. Biopsy samples were obtained during gastroscopy from macroscopically healthy tissue of the stomach or from healthy nasal epithelia during surgery. The specimens were incubated for 30–45 min at 37°C with a digestive solution. We obtained 1.5–8 × 10⁶ GM cells and 5–10 × 10⁵ NM cells per donor, both with viabilities of 80–95%. The cells were incubated in vitro for 1 hr at 37°C with the test compounds added in their appropriate solvents. In GM cells, we studied N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), sodium dichromate (Na₂Cr₂O₇), nickel sulphate (NiSO₄), cadmium sulphate (CdSO₄), and lindane. In NM cells, lindane was investigated. Each compound was assessed for DNA damaging activity in cells of at least three different human donor samples using the microgel single cell assay. Similar studies were performed with GM and NM cells obtained from Sprague-Dawley rats. We have found human GM cells to be more sensitive to the genotoxic activity of MNNG than rat GM cells (low effective concentration [LEC] = 0.16 and 0.625 μg/ml for human and rat, respectively). Human cells were also more sensitive to the cytotoxic/genotoxic activity of NiSO₄ (LEC = 5 and 19 μmoles/ml for human and rat, respectively). CdSO₄ was genotoxic in human GM cells (LEC = 0.03–0.125 μmoles/ml), whereas no dose-related genotoxicity was observed in rat GM at concentrations up to 0.5 μmoles/ml. In contrast, approximately equal responses regarding genotoxicity and cytotoxicity were observed in rat and human GM for Na₂Cr₂O₇ (0.25–1 μmoles/ml). Lindane, however, was genotoxic in three out of four rat GM but not in human GM cells (0.5–1 μmoles/ml), whereas it was active in both rat and human NM cells. Together with other recently published in vivo findings, our results with lindane can be interpreted according to a parallelogram approach. In view of possible human exposure situations and the sensitivities of the two target tissues from both species, the data imply that lindane will pose a health risk to humans by inhalation but not by ingestion. © 1994 Wiley-Liss, Inc.     

Doxorubicin-loaded microgels composed of cinnamic acid–gelatin conjugate and cinnamic acid–Pluronic F127 conjugate

Microgels were prepared by cinnamic acid–gelatin (type B) conjugate (CA-GelB) and cinnamic acid–Pluronic F127 conjugate (CA-Plur). ¹H NMR confirmed that CA was conjugated to gelatin and the gelatin to CA residue molar ratio was estimated to be 1:4.7 by a colorimetric method. CA-Plur of which the CA residue to Plur molar ratio was 1.2:1 was used as a thermo-sensitive polymer. The CA residues of CA-Plur/CA-GelB mixture were readily photo-dimerized to form microgels by UV irradiation. The isoelectric point of the microgel was found to be pH 5.8 and the hydrodynamic diameter decreased when the suspension temperature increased. The microgel could hardly retard the release of doxorubicin (DOX) at pH 3.0 and pH 5.0, but it could suppress and control the release at pH 7.4 possibly due to electrostatic attraction. Meanwhile, the release of DOX at pH 7.4 was less suppressed when the medium temperature was higher, possibly because of thermal thinning of Pluronic chain layer.     

铁缺乏对鼠肝癌前期病变影响的实验研究

利用大白鼠复制肝癌前病变发生的动物摸型，观察铁缺乏在肝癌发生的第二阶段，既癌前病灶转化为增生结节过程中的作用。结果发现：铁缺乏组中，可能转变为癌的ＧＧＴ染色阳性的持续性结节及ＨＥ染色的肝细胞增生性细节数显著减少。提示铁缺乏在肝癌前病灶转化为增生结节的过程中有抑制作用。