小鼠甲状腺肿发生率与碘的剂量反应关系

目的：研究小鼠甲状腺肿发生率与碘的剂量反应关系，确定引起小鼠10％、50％、90％甲状腺肿大率的水碘浓度，为动物高碘实验选用合适碘剂量提供参考依据。方法：用随机区组实验设计方法将初断乳昆明小鼠随机分为7组，用碘酸钾配制成含碘50μg/L的适碘对照组和250，500，1000，1500，2000，3000μg／L的高碘组，喂养100d后，观察各组甲状腺绝对、相对重量，组织形态学改变和甲状腺肿发生率.结果：①当水碘浓度在50－3000μg/L之间时，甲状腺绝对，相对重量与碘剂量呈明显的正相关，250μg/L组与对照比较差异有显著意义；②水碘浓度在250－3000μg／L之间时，小鼠甲状腺肿大率与碘剂量亦存在明显 的正相关关系，且引起小鼠10％、50％、90％甲状腺肿大率的水碘浓度分别为250，1500，3000μg/L。结论：饮水碘浓度在250－3000μg/L时，甲状腺肿大率与碘剂量呈明显的剂理反应关系，且引起小鼠10％、50％、90％甲状腺肿大率的水碘浓度分别为250，1500，3000μg/L，当饮水碘浓度为250μg/L时，即可引起小鼠胶质性甲状腺肿。     

富砷饮水暴露剂量与反应关系

为了解饮水型砷中毒皮肤损害与饮水砷含量、砷暴露剂量的关系,调查了砷中毒病区常住居民７９３人,分析了饮水砷含量、总砷摄入量与患病率的关系。结果表明：皮损患病率与水砷含量、总砷摄入量与患病率的关系。结果表明：皮损患病率与水砷含量、总砷摄入量呈正的直线相关关系（ｒ＝０．９６０、ｒ＝０．６８３）并得出该关系的方程表达。总砷摄入量与患病率呈一定的剂量反应关系。     

氟铝剂量比例与氟中毒关系的实验研究

目的 在既往研究发现高氟、高铝联合危害基础上,探讨自然本底低水平铝含量条件下氟铝剂量不同比例与氟中毒类型和病情的关系。方法 动物实验,以饲料中本底铝（Al)含量（45mg/kg)为基准,加入氟化钠（F）,设置4个染毒组（F：Al分别为1：2,1：1,2：1,3：1）和一个对照组,实验期限100d。结果 ①各染毒组骨铝含量均高于对照组,且随摄氟量增加而增加,骨密度（BMD）则呈降低趋势;②F：Al为2：1时,大鼠呈小细胞低色素性贫血。结论 氟铝联合作用具有普遍性,铝是影响氟中毒病情及氟骨症表现类型的因素之一。     

剂量反应曲线斜率在支气管哮喘中的诊断价值

目的探讨剂量反应曲线斜率(DRS)对支气管哮喘的诊断价值。方法对101例支气管激发试验阳性患者随访2年,4例失访,将患者分为两组,其中56例患者临床确诊为支气管哮喘,为哮喘组;41例未诊断哮喘的患者为非哮喘组。计算DRS,用ROC曲线评价DRS在诊断哮喘中的敏感性和特异性。结果ROC曲线下面积为81.8%,DRS最佳截点为22.28,敏感度为62.5%,特异度为92.7%。结论支气管激发试验阳性联合DRS可提高支气管哮喘诊断的特异度。     

碘的诱变性研究

本文以 Sty、SCE 二项试验方法研究了碘的诱变性,并应用 CPBS 法进行了初步致癌危险性评价。结果表明:碘含量在0.1～3.0mg 浓度下均为阴性,未呈现出诱变性。不致癌的危险性大于98%。并发现细胞增殖周期随碘的浓度增加 M_1期百分比缩短,而 M_3期则明显延长,提示碘可促使细胞增殖周期加速。     

胰岛素抵抗与心血管病危险因素个体聚集性的剂量-反应关系

目的 探讨中国人群胰岛素抵抗与心血管病危险因素个体聚集性之间的关系。方法 对北京石景山地区农民、首都钢铁公司工人共3899人（年龄35－64岁）的空腹胰岛素与空腹血糖、血压、血脂、血尿酸之间的关系进行调查。结果 由低至高胰岛素四等分组的心血管病危险因素个体聚集率分别为18.89%、28.03%、40.2%、49.49%（x^2MH=227.34,P=0.001），经多元logistic回归调整年龄、性别、工农、体重指数、吸烟、饮酒等因素后，显示第2、3、4等分组与第1组比较的优势（OR）及其95％可信区间分别为1.7(1.4-2.2),3.1(2.5-3.9),4.6(3.7-5.7）。结论 在中国人群中胰岛素抵抗与心血管病危险因素个体聚集呈剂量－反应关系，随着胰岛素水平的升高，个体发生危险因素聚集的风险性逐渐增高。     

氟化钠与小牛胸腺DNA直接结合作用的研究

目的 探讨氟化钠与DNA的直接结合作用。方法 应用自动程序升温紫外分光光度计和高效液相LC-VP离子色谱分析仪对氟化钠与小牛胸腺DNA的直接结合作用进行了研究。结果 6.3,483.0,987.0mg/L氟化钠对5.0,10.0,22.5mg/L小牛胸腺DNA在260nm的吸收光谱未造成任何影响，在205nm处吸收峰虽有随氟化钠浓度升高而逐渐降低的倾向，但结果的可重复性较差：1.0mg/L的溴化乙锭可使10.0mg/L浓度的小牛胸腺DNA融点温度显著升高，而210.0mg/L的氟化钠对其无明显影响；不同浓度小牛胸腺DNA与氟化钠作用后，冰乙醇变性洗涤，经高效液相色谱分析仪检测，DNA水溶液中无氟离子检出。结论 氟化钠未与小牛胸腺DNA发生稳定结合。     

中老年人群脂质蓄积指数与新发高血压的剂量-反应关系

目的:探讨中老年人群脂质蓄积指数(LAP)与高血压患病的剂量-反应关系。方法:选取中国健康与退休纵向研究(CHARLS)2011年的基线数据及2015年的追踪数据。采用多因素Logistic回归模型探讨LAP与新发高血压之间的关系。通过建立3个模型来矫正调整8个因素(年龄、性别、受教育程度、居住地点、婚姻状况、吸烟状况、饮酒状况和睡眠时间)对结果造成的潜在可能影响,并限制立方样条模型来检查可能的非线性关联,将LAP与高血压患病的剂量-反应关系可视化。结果:共纳入合格参与者4 808人,其中新发高血压823人,LAP最高组(Q₄)新发生高血压的风险最高117%[OR=2.17,95%CI(1.56,2.47)]。使用限制性三次样条回归分析显示,LAP与高血压发病率之间存在剂量反应关系(P<0.001),且为非线性关系(P<0.001)。将LAP作为连续性变量进行计算,在调整潜在混杂因素后,LAP每上升1个四分位数,新发生高血压的患病风险增加5%。结论:LAP为高血压的危险因素且二者存在剂量-反应关系,LAP可作为筛查中老年人新发高血压患病风险的有效指标。     

咖啡与脑卒中风险的剂量-反应Meta分析

目的:用Meta分析方法评估咖啡与脑卒中风险之间的关系。方法:计算机检索Pubmed、EMBASE、Cochrane图书馆、中国生物医学文献、中国知网、万方和维普数据库,收集关于咖啡与脑卒中风险关系的前瞻性队列研究,由2位研究员按纳入排除标准独立筛选文献、提取资料并用卡斯尔-渥太华量表(NOS)评价文献质量。用Stata/SE 15.0软件进行统计分析。结果:共纳入17项前瞻性队列研究、1142274例受试者,其中包括83433例脑卒中患者。Meta分析结果显示,咖啡可明显降低脑卒中风险(RR=0.80,95%CI:0.75~0.85),但并不能降低日本人群的脑卒中风险。剂量-反应Meta分析显示,咖啡摄入量与脑卒中风险之间呈非线性关系(非线性P值<0.001)。与从不喝咖啡者相比,每天喝2、4、6、8杯咖啡者的脑卒中相对风险分别为0.87(95%CI:0.82~0.92)、0.83(95%CI:0.76~0.90)、0.84(95%CI:0.74~0.95)、0.86(95%CI:0.72~1.03)。结论:咖啡摄入量与脑卒中风险呈非线性关系,适量摄入咖啡与脑卒中风险呈负相关,每天喝4~5杯咖啡时脑卒中风险最低。但现有的研究证据不能证明喝咖啡能明显降低亚洲人群的脑卒中风险。     

生理浓度范围内血清总胆红素水平与脑卒中发病风险之间关系的剂量-反应Meta分析

目的:用Meta分析方法定量评价生理浓度范围内血清总胆红素水平与脑卒中发病风险之间的剂量-反应关系。方法:计算机检索PubMed、Embase、The Cochrane Library、Web of Science、中国知网、中国生物医学文献数据库、万方和维普数据库,查找符合纳入标准的临床研究。应用STATA 11.0软件进行统计分析。结果:纳入11项观察性研究、202641例受试者,其中包括4904例脑卒中患者。Meta分析结果显示,血清总胆红素水平与缺血性脑卒中及脑卒中发病风险呈负相关[OR(95%CI)分别为0.76(0.6~0.87)和0.74(0.64~0.86),P均<0.001]。剂量-反应Meta分析显示,随着血清总胆红素水平升高,脑卒中发病风险逐渐降低;血清总胆红素水平每增加1μmol/L,缺血性脑卒中及脑卒中发病风险分别降低1.2%(OR=0.988,95%CI:0.981~0.996,P=0.002)和1.5%(OR=0.985,95%CI:0.979~0.992,P<0.001)。结论:生理浓度范围内血清总胆红素水平与脑卒中发病风险呈线性负相关。     

Oxidative/antioxidative effects of different lignin preparations on DNA in hamster V79 cells

Endogenous oxidative damage to DNA is thought to be an important etiologic factor in the development of chronic diseases such as cancer. Many products of the vegetable kingdom have been suggested to limit oxidative damage to DNA in humans. To this group belong lignins, polyphenols present in all plants (including edible plants). The aim of this study was to examine oxidative/antioxidative effects of different lignin preparations on mammalian DNA. In addition to a water-soluble sulfur-free lignin 1 which was obtained by fractionation of hardwood hydrolysate, we investigated lignin 2 (obtained by oxidation of lignin 1), lignin 3 (prepared by the extraction of lignin 2 with a mixture ethanol-water 3:1), lignin 4 (Na-salt of lignin 3) and lignin 5 (prepared by extraction of lignin 2 with diethylether). Our results showed that only the original lignin 1 did not increase substantially the level of DNA damage. Lignins 2, 3, 4 and 5 increased both the level of frank DNA strand breaks + alkali-labile sites and the level of FPG-sensitive sites representing oxidative damage to DNA. Lignin 1 was further tested for its antioxidative activity against DNA base modifications generated by visible light+photosensitizer. Obtained results confirmed the oxygen species-scavenging activity of lignin 1.     

温石棉及其代用纤维对V79细胞p16和p53表达的影响

目的研究温石棉及其代用纤维对中国仓鼠肺细胞（V79细胞）p16及p53表达的影响,探讨温石棉及其代用纤维的致癌机制。方法将不同种类（四川新康温石棉、陕西陕南温石棉、玻璃纤维、陶瓷纤维、硅灰石、岩棉）及不同浓度（1-10 mg/L）的温石棉及其代用纤维暴露于V79细胞中,并设阴性对照。采用免疫组化SABC法检测V79细胞p16及p53的表达,并进行比较。结果与阴性对照比较,各染毒V79细胞中的抑癌基因p16和p53表达下调,P均〈0.05;随着温石棉及其代用纤维暴露浓度的增加,V79细胞p16和p53的表达减弱,其OD值也呈下降趋势（P均〈0.05）。结论温石棉及其代用纤维均有不同程度的致癌性;其诱导癌症发生的机制可能与下调抑癌基因p16和p53表达有关。     

水氟与骨密度和骨钙素的剂量效应关系研究

目的 分析水氟与骨密度(BMD)、血清骨钙素(BGP)的剂量-效应关系,探讨BMD和血清BGP作为氟中毒早期骨损伤筛查指标的可能性.方法 2006年选择江苏省宿迁市地方性氟中毒重病区村瓦庙村(氟接触组)103例和非病区村新淮村(对照组)43例居民,调查性别、年龄、身高、体质量,测定家庭手压井水氟、BMD及血清BGP水平.根据水氟四分位间距进行分组,分析水氟与BMD和血清BGP的关系,应用Curve Expert 1.3软件拟合水氟与BMD、血清BGP异常率的剂量-效应关系方程.结果 氟接触组的男、女性家中的饮水氟[(2.38±0.68)、(2.62±0.91)mg/L]均高于对照组[(0.35±0.08)、(0.36±0.07)mg/L],组间比较差异均有统计学意义(t值分别为14.27、11.08,P均<0.01);氟接触组男性BMD[(0.78±0.07)g/cm2]低于对照组[(0.83±0.08)g/cm2],组间比较差异有统计学意义(t=2.37,P<0.05).氟接触组男性、女性的血清BGP[(4.17±0.67)、(4.11±0.57)μg/L]均高于对照组[(1.48±0.40)、(1.44±0.39)μg/L],组间比较差异有统计学意义(t值分别为17.64、19.40,P均<0.01).水氟≥2.92 mg/L组的BMD[(0.66μ0.15)g/cm2]低于<0.42 mg/L组[(0.76±0.12)g/cm2],组间比较差异有统计学意义(P<0.01).水氟0.42～、2.05～、≥2.92 mg/L组的血清BGP[(3.83±1.07)、(4.22±0.72)、(3.99±0.63)μg/L]均高于<0.42 mg/L组[(1.44±0.37)μg/L],组间比较差异均有统计学意义(P均<0.01);水氟与BMD异常率的剂量-效应关系方程为Y=(0.284-0.058x)-<'1.260>,r=0.999 94;水氟与血清BGP异常率的剂量-效应关系方程为Y=100.05/(1+78.62e<'-4.55x>),r=0.99999.结论 水氟与BMD、血清BGP均有剂量-效应关系,BMD和血清BGP有可能作为氟中毒特别是骨损伤的敏感筛查指标.     

Effect of cytosine arabinoside and hydroxyurea on micronucleus formation induced by model clastogens in Chinese hamster V79 cells

Post-cultivation of treated cells in the presence of DNA repair inhibitors has been proposed as a new methodological approach of the micronucleus (MN) assay to increase the sensitivity of this technique. In order to assess the advantages and limitations of this promising methodological approach, several genotoxic/clastogenic agents with different mechanisms of activity were chosen to assess the effect of DNA repair inhibitors on the level of micronuclei (MNi) induced by particular agent using Chinese hamster V79 cells. Both UV light (UV) and benzo(a)pyrene (BaP) increased significantly the micronucleus level in V79 cells (p<0.01-0.001). In contrast, only at cytotoxic concentration (>0.8 mM) a slight but statistically significant rise of MNi was determined in cells exposed to N-methyl-N-nitroso urea (MNU). However, post-cultivation of MNU-treated cells in the presence of DNA repair inhibitors (cytosine arabinoside, AraC and hydroxyurea, HU) led to an additional rise of MNi. While AraC had a synergistic effect on MN formation (0.4 mM and 0.8 mM, DS=2.14 and 1.13, respectively), HU had less than additive effect (DS=0.86 and 0.66) and the combined treatment of cells with AraC and HU was least effective (Cf=0.36 and 0.28). On the other hand, post-cultivation of UV- and BaP-treated cells in the presence of AraC did not result in any synergistic effect on MN formation. No effect or even a decrease of MNi was measured particularly due to HU or combined treatment of HU and AraC. Incubation of control untreated cells with AraC gave rise to a significant increase of MN formation (2- to 2.5-fold) as well. Hydroxyurea or the combined treatment of HU with AraC had lower effect on the spontaneous level of MNi. Our study shows, that the combination of MNU treatment with DNA repair inhibitors increased the number of MNi on well proliferating V79 cells; in case UV light and BaP treatment, the involvement of DNA repair inhibitors did not contribute to an increase of sensitivity of MN assay. On the basis of our results we suppose that the AraC/CBMN assay might be a promising approach in genetic toxicology applied only to lymphocytes.     

High-level expression of enzymatically active mature human gamma-glutamyltransferase in transgenic V79 Chinese hamster cells.

gamma-Glutamyltransferase [GGT; (5-glutamyl)-peptide:amino-acid 5-glutamyltransferase, EC 2.3.2.2] is a glutathione-metabolizing enzyme, whose activity variations in serum and organs are valuable markers of preneoplastic processes, alcohol abuse, and induction by xenobiotics. To elucidate the implication of GGT in various metabolic pathways, we established a stable transgenic V79 cell line, highly producing the human GGT. A full-length cDNA, encoding the human hepatoma HepG2 GGT, was subcloned in an expression vector under the control of the simian virus 40 early promoter and was used to transfect V79 cells. We selected a cell line exhibiting a GGT activity of 2 units per mg of protein, the highest GGT expression level reported to date. As described for the human kidney and liver enzymes, the recombinant GGT purified from this cell line showed a heterodimeric structure. Its two subunits existed as sialylated and differentially glycosylated isoforms, with mean molecular masses of 80 and 29 kDa. However, catalytic features were found to be identical to those of human serum and HepG2 GGTs. The newly engineered cell line thus should be useful for the production of human GGT and as a potential alternative model for pharmacological studies.     

Genotoxicity of Fusarium mycotoxins (nivalenol, fusarenon-X, T-2 toxin, and zearalenone) in Chinese hamster V79-E cells in vitro

The mycotoxins nivalenol, fusarenon-X, T-2 toxin and zearalenone were checked for clastogenic damage, induction of SCEs and cell cycle delay in Chinese hamster V79-E cells in vitro. The trichothecenes nivalenol, fusarenon-X and T-2 toxin provoked a marked toxicity as especially expressed by cell cycle delay. As compared to toxicity, they are weak clastogens. Addition of S9 mix toxified nivalenol, detoxified T-2 toxin and had no marked influence on fusarenon-X activity. SCE values were slightly increased. It is suggested that the effects observed are unspecific and are caused by inhibition of protein synthesis. Zearalenone was inactive in the three assays. Problems of genotoxicity and carcinogenicity of Fusarium toxins are discussed.     

氟化钠对原代培养大鼠甲状腺细胞形态学的影响

目的 观察不同染氟(氟化钠)剂量对体外培养原代SD大鼠甲状腺细胞形态学的影响,为探讨氟引起甲状腺组织损伤提供理论依据.方法 采用原代细胞培养方法,体外培养SD大鼠甲状腺细胞,96 h后收集对数生长期的细胞,将细胞密度调整约5.0×108个/L;取5 ml(约 2.5×106个细胞)加入到6孔培养板中,培养12h,按不同染氟剂量分为0(对照)、10、100、1000 μmol/L组,每组设6个重复样.相差显微镜下观察甲状腺细胞的形态变化.48 h后收集细胞,扫描电镜下进行甲状腺形态学观察和分析.结果 相差显微镜下,对照组甲状腺细胞透明度良好.聚集成群,贴壁良好,细胞存活率在90%以上;染氟组甲状腺细胞有大量悬浮,透明度差,细胞存活率约55%.扫描电镜下,可见对照组甲状腺细胞胞膜完整,细胞之间嵌合紧密,界限清晰,分裂良好;10、100μmol/L组甲状腺细胞明显皱缩和变形;1000μmo/L组甲状腺细胞胞膜不完整,集结在一起生长的细胞间界限不明显,有的细胞发生明显皱缩,有的细胞则完全破碎.结论 氟影响甲状腺细胞的生长和发育,使细胞的形态发生改变,损伤程度与剂量有关.     

Stable expression of rat cytochrome P-450IIB1 cDNA in Chinese hamster cells (V79) and metabolic activation of aflatoxin B1.

V79 Chinese hamster fibroblasts are widely used for mutagenicity testing but have the serious limitation that they do not express cytochromes P-450, which are needed for the activation of many promutagens to mutagenic metabolites. A full-length cDNA clone encoding the monooxygenase cytochrome P-450IIB1 under control of the simian virus 40 early promoter was constructed and cointroduced with the selection marker neomycin phosphotransferase (conferring resistance to G418) into V79 Chinese hamster cells. G418-resistant cells were selected, established as cell lines, and tested for cytochrome P-450IIB1 expression and enzymatic activity. Two cell lines (SD1 and SD3) were found that stably produce cytochrome P-450IIB1. Although purified cytochromes P-450 possess monooxygenase activity only after reconstitution with cytochrome P-450 reductase and phospholipid, the gene product of the construct exhibited this activity. This implies that the gene product is intracellularly localized in a way that allows access to the required components. If compared with V79 cells, the mutation rate for the hypoxanthine phosphoribosyltransferase (HPRT) locus in SD1 cells is markedly increased when exposed to aflatoxin B1, which is activated by this enzyme.     

氟对原代培养大鼠肝细胞的氧化损伤作用研究

目的探讨氟对原代培养大鼠肝细胞的氧化损伤作用。方法采用半原位酶消化法分离大鼠肝细胞，氟化物染毒24h后用噻唑蓝(MTT)比色法检测细胞存活率，检测培养液中谷丙转氨酶(ALT)、谷草转氨酶(AST)的活性及脂质过氧化产物丙二醛(MDA)的含量。结果氟对大鼠肝细胞具有明显的毒性作用，表现为细胞存活率下降，ALT、AST的活性升高，MDA含量增加。结论脂质过氧化引起的氧化损伤作用是氟致原代培养大鼠肝细胞毒性的主要原因。     

Role of sodium influx in thyrotrophin action: effects of the sodium channel agonist veratridine and thyrotrophin on radioiodine turnover and membrane potential in cultured porcine thyroid cells

Veratridine, a sodium channel agonist, depolarized cultured thyroid cells and increased the secretion of radioiodine from the organically bound pool. These effects were similar to those of TSH. Depolarization of the cells by increasing the potassium concentration of the medium failed to promote secretion, indicating that the sodium influx, rather than the depolarization itself, mediated the response. Veratridine, like TSH, also acutely reduced the cells' iodide uptake and inhibited the iodide transport pump. Unlike TSH, however, veratridine reduced, rather than increased, the fractional exit rate of iodide anion from the unbound pool. The data are consistent with the hypothesis that a sodium influx mediates some but not all of the actions of TSH on the thyroid gland, including the stimulation of secretion of thyroid hormones.