肝癌高发区水体污染的微核效应及其致癌危险性研究

将紫露草微核试验和流行病学调查相结合,本研究首次发现:在扶绥肝癌高发区居民饮用的塘水中,有致植物细胞染色体损伤的化学诱变剂污染。这些化学诱变剂的存在,提高了当地届民患肝癌的潜在危险性,很可能是导致居民肝癌高发的又一重要原因。     

肝癌高发区饮用塘水的诱变性和遗传毒性研究

采用生物学检测技术，对广西某肝癌高发区的８３份饮用水进行了诱变性评价，并分别对四组饮用塘水和非塘水的１２９名成年男性居民和２１３名儿童进行了细胞遗传毒性损伤的分析。结果：各类饮用水的诱变性阳检率为４５．７８％，其中，塘水的阳检率高达９３．３３％（２８／３０），而深井水全部为阴性（０／９）。塘水中存在的化学诱变程序控制物质对紫露草花粉母细胞和鱼周血细胞均具有潜在的遗传毒笥。从幼年即已开始饮用塘水的儿     

肝癌高发区饮水诱变性及干预措施的研究

采用紫露草微核试验(TradescantiaMicronucleus Test),作者在我国肝癌高发区扶绥县进行了居民饮用水诱变性的测定和干预措施的研究,本文将报告这方面的研究结果。     

硒与癌变的微观水平研究

流行病学研究和动物实验证明,硒与多种人类癌症的发病率呈负相关,并能抑制实验动物自发性、移植性和化学致癌剂诱发的肿瘤。治疗剂量的硒还能抑制艾氏腹水癌细胞和白血病L_(1210)细胞在小鼠体内扩散,使小鼠的存活期显著延长。上述宏观领域的研究都支持硒具有抗癌作用的假设,但硒的抗癌机制目前尚不清楚。近年来,细胞遗传学、分子遗传学和遗传毒理学等基础学科的飞速发展,为硒的抗癌机制研究提供了理论依据和技术方法。现将该领域的研究进展综述如下。一、硒与程序外DNA 修复(Unschedul-ed DNA Synthesis,UDS)UDS 是细胞非增殖期的一种DNA 修复合成,它能反映DNA 受损伤的程度,并与化学物质的诱癌性有一定的相关。Lo 等(1978)报道,10~(-5)～10~(-3)的亚硒酸钠(Na_2SeO_3可诱导人皮肤纤维母细胞的DNA 断裂、UDS和染色体畸变,与鼠肝S9组分共同温育后该效应显著增强。但硒酸钠(Na_2SeO_4)不     

几种抗致癌物对环磷酰胺致小鼠骨髓微核的影响

本文报告几种抗致癌物[维生素A酸(RA)、二丁基烃基甲苯(BHT)、β-萘黄酮(βNF)及亚硒酸钠(Na_2SeO_3)]对环磷酰胺(CP)致C57小鼠骨髓微核的影响及可能的机理。RA150mg/kg灌胃4天、BHT600mg/kg灌胃4天、βNF80mg/kg灌胃2天和Na_2SeO_320ppm饮水7天可抑制CP(30mg/kg腹腔注射一次)致小鼠骨髓多染红细胞微核率分别至CP对照组的70.7％、13.8％、67.5％及     

肝癌高发区饮用塘水浓缩物诱发人肝细胞非程序DNA合成的研究

利用人原代肝细胞非程序ＤＮＡ合成试验（ＵＤＳ）对广西某肝癌高发区的居民饮用塘水浓缩物进行检测，结果发现：塘水浓缩物的浓度在０．１０ｍｇ／ｍｌ－０．５０ｍｇ／ｍｌ时，可诱导人肝细胞ＵＤＳ反应，对ＤＮＡ具有明显的损伤作用，且显示出一定的剂量一效应关系，表明塘水中存在有基因毒性物质，提示该地区居民的肝癌高发与长期饮用糖水有关。     

肝癌高发区不同水体对健康人微核率的影响

应用微核检测技术，研究不同类型饮用水诱发健康人外周血淋巴细胞的微核效应，结果表明：①不同饮用水的细胞毒作用依次为宅沟水＞泯沟水＞自来水＞重蒸水，其微核诱变效应为泯沟水＞自来水＞重蒸水。②不同饮用水诱发的微核率与饮用相应类型水的居民的肝癌发病率呈平行关系。进一步证实了肝癌高发区饮用水与原发性肝癌的发生密切相关。提示饮用深井水、改进饮水质量是一项行之有效的干预性措施；如能长期坚持，对预防肝癌有着积极的意义。     

肝癌高发区扶绥县饮用水对蚕豆根尖微核的致突变效应

应用蚕豆根尖微核技术测定了肝癌高发区扶绥县饮用水的致突变性。结果表明，２５份饮用水样中有１２份塘水能明显诱导蚕豆根尖微核率的增高，提示饮用塘水中存在致植物染色体畸变的物质，摄入这类物质可能是增加当地居民患肝癌的潜在危险，从而为肝癌的饮水污染病因理论提供实验佐证。     

实验性胃癌的化学预防—微量元素硒、锰对实验性小鼠胃癌的影响及其胃组织硒锰水平的分析

大量研究证明硒是一个有效的抗癌剂。但对锰的抗癌效应了解甚少。而硒与锰有无协同作用则未见报道。本项研究的目的是观察硒、锰和硒+锰对3-甲基胆蒽诱发小鼠胃癌的影响。动物胃癌模型是按胡素坤改良方法(1977)建立的。硒(Na_2SeO_3,1.3ppm)和锰(MnSo_4,7.8ppm)是加至饮水中喂养小鼠,实验16周结束时,处死各组动物,进行病理学检查和胃组织的硒、锰水平分析。给甲基胆蒽者发癌率为58％,单纯加硒或锰     

城市饮用水的致突变性检测

城市饮用水的致突变性检测曹明富，管利红，应燕儿（杭州师范学院１００３６）城市饮用水中的有机物污染及加氯消毒对人体健康潜在致突变致癌变效应，早已引起人们的的关注。从１９９１年开始．我们采用改进的紫露草四分体微核试验法，在对京杭大运河杭州段和西湖水等进行...     

Effect of sodium selenite on the chromosomal aberration of V 79 cells induced in vitro by MNNG and MNU

Effect of sodium selenite on chromosomal aberration of V 79 cells induced by MNNG and MNU was studied. Na2SeO3 alone, at the concentration of 10(-7)-10(-4) M, increased the incidence of chromosomal aberration. However, Na2SeO3 at 10(-7)-10(-5) M, having been preincubated with the cells for 4 hours, could reduce the number of cells with chromosomal aberration induced by MNNG. Na2SeO3 at 10(-7)-10(-4) M inhibited mutagenic activity of chromosomal aberration induced by MNU. The same inhibition was observed even sodium selenite was added to the medium simultaneously with this carcinogen. The results indicate that sodium selenite alone, at the concentration range used in this experiment, is an aberration-inducing agent. But when combined with the carcinogen, anti-cancer effect is obtained.     

Chemoprevention of experimental mammary carcinogenesis by the synthetic organoselenium compound, benzylselenocyanate, in rats

The effect of the dietary organoselenium compound, benzylselenocyanate (BSC) along with its sulphur analogue, benzylthiocynanate (BTC) and sodium selenite (Na2SeO3), on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis was examined in female Sprague-Dawley rats during the initiation phase of carcinogenesis. Semipurified diets containing 25 p.p.m. of BSC and 25 p.p.m. BTC, and 4 p.p.m. Selenium as Na2SeO3 in drinking water were given to 5-week-old rats for 3 weeks starting 2 weeks before, during and until 1 week after carcinogen treatment. At 7 weeks of age animals were given a single dose of DMBA (10 mg) in 1 ml olive oil by oral intubation. One week after DMBA treatment, the groups receiving BSC- and BTC-supplemented diets were transferred to the unsupplemented standard diets and the group of rats receiving Na2SeO3 in drinking water was transferred to regular tap water for the duration of the experiment. The results indicate that the rats receiving BSC in their diet showed a highly significant inhibition of tumor incidence and tumor multiplicity as well as a prolonged latency period when compared to the group fed the control diet. Neither BTC nor Na2SeO3 had any effect on the subsequent development of mammary tumors. These results indicate that dietary BSC inhibits mammary tumor incidence during the initiation phase of carcinogenesis and is a considerably more potent inhibitor than its sulphur analogue BTC and inorganic selenium. This is the first report that demonstrates the inhibition of mammary carcinogenesis by a synthetic organoselenium compound.     

The effect of sodium selenite on cell proliferation and transformation of primary rat tracheal epithelial cells.

The effects of sodium selenite (Na2SeO3) on cell proliferation and the development of preneoplastic transformed variants were studied in primary cultures of rat tracheal epithelial cells. Results revealed a biphasic effect of Na2SeO3 on cell proliferation: at concentrations between 6 x 10(-8) and 6 x 10(-6) M, it stimulated and at concentrations of approximately 2 x 10(-5) and above it inhibited cell proliferation (presumably due to toxicity). Nontoxic concentrations of Na2SeO3 (6 x 10(-8) -6 x 10(-7) M) significantly reduced the spontaneous transformation frequency. Transformation induced by the tobacco-specific nitrosamine 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was effectively inhibited by nontoxic as well as toxic concentrations of Na2SeO3. Treatment of cultures with Na2SeO3 after cessation of NNK exposure, i.e. during the selection period, also significantly reduced the transformation frequency. These experiments show that the inhibition of transformation by Na2SeO3 is not the result of an antiproliferative effect. They further indicate that the inhibitory effect occurs even when the chemical treatment occurs during the 'postinitiation' phase. Thus the inhibition of transformation by Na2SeO3 cannot solely be explained by its effects on drug metabolism.     

亚硒酸钠和维甲酸联合对HL-60细胞c-myc和c-fos基因表达的影响

 以HL-60细胞为实验对象，利用Slot-blot技术，观察了亚硒酸钠和维甲酸（RA）联合对其原癌基因c-myc和c-fos表达的影响。结果表明：硒和RA在第一和第二天都可使c-myc基因表达下降，以后逐渐上升到对照组或稍高水平。联合可使c-myc表达显著下降，强于两单独作用。硒和pA在第三至第四天均可使c-fos表达明显升高，第四天5.8ｕmol/L Na₂SeO₃ 和0.1ｕmol/LRA以及联合组c-fos表达水平分别为对照组的2.8，3.7和5.4倍。     

富硒大蒜对体内外人胃癌细胞生长的影响

目的 比较富硒大蒜、普通大蒜、亚硒酸钠以及普通大蒜与亚硒酸钠混合（蒜硒联合）处理影响人胃癌细胞生长的能力。方法 利用细胞计数、流式细胞术、Western blot和裸鼠瘤体积测定等方法,观察富硒大蒜水溶物对离体培养的MGC803胃癌细胞系及其在裸鼠皮下生长的影响。结果 （1）在离体条件下,富硒大蒜对MGC803细胞增殖有明显抑制作用,与等蒜量普通大蒜作用强度相似;等硒量亚硒酸钠抑制作用最弱,蒜硒联合抑制作用最强。（2）富硒大蒜、普通大蒜和亚硒酸钠处理24h后,未同步化的细胞G1期增多,已同步化的细胞S期增多;蒜硒联合处理则使未同步化和已同步化细胞G2＋M期增多。（3）4种处理24h后,同步化细胞的Cdk2-CyclinE和Cdk4-CyclinD1复合物蛋白含量均降低。（4）饲喂Balb/C裸小鼠含1．67％富硒大蒜粉（含硒2μg/g)的饲料,对移植瘤生长的抑制率达29．92％;0．83％富硒大蒜、1．67％普通大蒜和4．38μg/g亚硒酸钠（含硒2μg/g)处理组未见明显抑制作用。（5）0．83％富硒大蒜处理可诱发裸鼠单核细胞包裹肿瘤。结论 富硒大蒜能够抑制MGC803细胞在体外的生长,主要作用在于蒜。富硒大蒜对裸鼠移植胃癌有抑制作用,作用比普通大蒜和亚硒酸钠强。     

微量元素亚硒酸钠与硫酸镍对Epstein—Barr病毒壳抗原表达影响的研究

本文报告应用间接免疫荧光技术,研究了亚硒酸钠与硫酸镍对EB病毒壳抗原(VCA)表达的影响及其相互关系,0.1-1.0μg/ml亚硒酸钠1-20μg/ml硫酸镍,各自对VCA表达呈抑制和促进的相反效应。适当浓度的亚硒酸钠不仅能抵消各剂量硫酸镍对病毒抗原表达的促进作用,而且还明显抑制抗原自身的表达。时经镍预处理24小时后的靶细胞,硒仍显示出强烈的抑制效应:外一方面,硒一次预处理后,仍保持其对镍激发抗原能力的抑制。这些结果提示,硒对EBV-VCA表达的抑制作用远较镍的促进作用为强,而且持久。 本文还讨论了鼻咽癌患者体内的高镍低硒状态与EBV感染的相互关系及其可能在鼻咽癌发生、发展中所起的作用。     

Effects of vitamin E, vitamin B2 and selenite on DNA single strand breaks induced by sodium chromate (VI)

The effects of vitamin E, vitamin B2 and selenite on DNA single strand breaks induced by Na2CrO4 were examined by alkaline elution. Incubation of Chinese hamster V-79 cells with alpha-tocopherol succinate (vitamin E) for 24 h prior to exposure to Na2CrO4 resulted in a decrease of DNA breaks produced by this compound. However, similar pretreatment with riboflavin (vitamin B2) or Na2SeO3 resulted in an enhanced formation of breaks induced by Na2CrO4. Pretreatment with Na2SeO3 resulted in increased levels of glutathione in these cells while levels of glutathione remained the same with vitamin E or vitamin B2. These results suggest that Na2CrO4 induced DNA breaks appear to be mediated by the formation of free radicals and/or cellular reductive metabolism.     

Selenium effects on prostate cell growth.

Epidemiological and clinical data suggest that selenium may prevent prostate cancer, but the biological effects of selenium on normal or malignant prostate cells are not well known. We evaluated the effects of sodium selenite (Na2SeO3) or l-selenomethionine (SeMet) on monolayer and anchorage-independent growth in a series of normal primary prostate cultures (epithelial, stromal, and smooth muscle) and prostate cancer cell lines (LNCaP, PC-3, and DU145). We observed differential, dose-dependent growth inhibition and apoptosis within prostate cancer cells (compared with normal prostate cells) treated with 1-500 microM of Na2SeO3 or SeMet. Na2SeO3 more potently inhibited growth at any given concentration. The androgen-responsive LNCaP cells were the most sensitive to selenium growth suppression (IC50s at 72 h for Na2SeO3 and SeMet were 0.2 and 1.0 microM, respectively). Growth of the primary prostate cells virtually was not suppressed (IC50s at 72 h for Na2SeO3 and SeMet were 22-38 and >500 microM, respectively). We also observed that DNA condensation and DNA fragmentation (terminal deoxynucleotidyltransferase dUTP nick end labeling/fluorescence-activated cell sorting) were elevated in selenium-treated cells and that activated caspase-3 colocalized with terminal deoxynucleotidyltransferase dUTP nick end labeling-stained cells by immunofluorescence. Higher basal poly(ADP-ribose) polymerase (PARP) expression levels and PARP cleavage (a substrate for caspase-3) were observed during apoptosis in tumor cells, compared with normal cells. Selective tumor cell death was associated with an increase in sub-G0-G1 cells after propidium iodide staining and fluorescence-activated cell sorting analysis. SeMet caused an increase in arrest in the G2-M phase of the cell cycle selectively in cancer cells. Inhibition of cancer cell growth by SeMet was associated with phosphorylation of P-Tyr15-p34/cdc2, which caused growth arrest in the G2-M phase. Anchorage-independent growth of prostate cancer cells in soft agar was sensitive to selenium. Our results suggest that Na2SeO3 is the more potent inducer of apoptosis in normal and cancer prostate cells. Our SeMet results involving PARP and G2-M cell-cycle arrest (cited above) indicate that SeMet selectively induces apoptosis in cancer but not primary cells of the human prostate. Our overall findings are relevant to the molecular mechanisms of selenium actions on prostate carcinogenesis and help demonstrate the selective, dose-dependent effects of selenium (especially SeMet) on prostate cancer cell death and growth inhibition.     

亚硒酸钠对人早幼粒白血病细胞的RB蛋白磷酸化的影响

 以人早幼粒白血病细胞(HL－60)为实验对象,利用Western－blotting方法和流式细胞仪分析,研究亚硒酸钠对HL－60细胞的RB蛋白产物磷酸化的影响和探讨其抗癌机制。Western－blotting结果显示:与对照组相比,在第四天5.8μmol/LNa2SeO3可使磷酸化Rll蛋白减少49％,去磷酸化RB蛋白仅轻度增加,但在加硒组中去磷酸化RB蛋白占RB蛋白总量的71.1％。与此同时,细胞周期的结果表明:亚硒酸钠对HL－60细胞的G2＋M和S期有一定的阻滞。该实验在蛋白分子水平上研究了亚硒酸钠抑制HL－60细胞增殖的作用机制。     

Different effects of selenium on proliferation of human lung adenocarcinoma cells and human embryonic lung diploid cells in vitro

After treating human lung adenocarcinoma cells by Na2SeO3 (1 microgram/ml) for 24 hours, its mitotic index decreased by 50%. The reduction rate was directly proportional to selenite concentration (1-5 micrograms/ml). In the meantime, the labelling index, growth rate and progression of the cell cycle were also inhibited. In contrast to the above observation, there was no marked change in the cell count, mitotic index, labelling index and the average silver granule number in the human embryonic lung diploid cells treated by Na2SeO3 (1-5 micrograms/ml) for 1-3 days. When human embryonic lung diploid cells were mix-cultured with human lung adenocarcinoma cells in the presence of 5 micrograms/ml Na2SeO3 for 24 hours, the former maintained a normal morphology, while the lung cancer cells showed heavily vacuolated cytoplasms and distorted nuclei.