甲醛与苯对动物细胞的遗传学效应及联合毒性研究

目的探讨不同浓度的甲醛与苯对小鼠外周血红细胞、骨髓细胞微核的诱发效应。方法甲醛、苯及两者联合作用分高、中、低三个剂量组，采用静吸式染毒方法，每天2h，连续染毒15d，考查微核率的变化。结果染毒后小鼠外周血红细胞、骨髓PCE细胞微核率均明显升高，与对照组相比差异显著。结论甲醛和苯均可不同程度的影响小鼠外周血红细胞和骨髓细胞的微核细胞率，并呈现剂量效应关系，联合作用时效应最强。     

人造板材释放的甲醛对小鼠骨髓细胞微核率影响

目的 探讨不同浓度气态甲醛对暴露小鼠的骨髓嗜多染红细胞微核的诱发效应。方法用不同剂量气态甲醛对小鼠进行连续动态染毒处理72h，取小鼠骨髓细胞制片，观察小鼠骨髓嗜多染红细胞微核形成率，从而判断气态甲醛对小鼠骨髓嗜多染红细胞微核的诱发效应。结果经甲醛染毒处理后，小鼠骨髓嗜多染红细胞微核率逐渐升高，与对照组相比有极显著性意义。结论甲醛可不同程度地影响小鼠骨髓嗜多染红细胞的微核形成率，并呈良好的剂量一效应关系。     

四氯化碳对雄性小鼠的遗传毒性

目的检测环境污染物四氯化碳的诱变活性,评价其可能的潜在遗传毒性。方法21只雄性昆明种小鼠随机分成7组,每组3只,其中1组为对照组,其余6组采用腹腔注射的方法,分别用5、15、25mg/kg四氯化碳进行染毒24h和48h分别进行精子畸形试验和小鼠股骨骨髓嗜多染红细胞(PCE)微核试验,然后每组观察5000个精子计算精子畸变率;每组观察5000个股骨骨髓PCE细胞,计算微核率。结果染毒小鼠的精子有明显的畸变效应,小鼠股骨骨髓PCE细胞的微核率和精子畸变率明显高于对照组(P<0.01)。结论四氯化碳对小鼠生殖细胞和血红细胞有遗传毒性作用。     

硒和锗拮抗苯致小鼠骨髓细胞微核的实验观察

采用小鼠骨髓嗜多染红细胞微核试验方法观察微量元素硒和锗的抗苯诱变活性。结果：苯吸入染毒（１５ｍｇ／Ｌ×５天，每天２小时）后，小鼠微核率明显增高。在苯处理前３０分钟经口给予不同浓度的亚硒酸钠（００５～２５０ｍｇ／ｋｇ）或锗－１３２（５０～５００ｍｇ／ｋｇ），微核细胞率显著降低，微核抑制率随硒或锗剂量的增加而升高。提示，硒和锗对苯诱导的遗传物质损伤具有保护作用     

环磷酰胺诱导小鼠骨髓细胞微核的影响因素的研究

[目的]研究环磷酰胺（Cyclophosphamide，CP）诱导小鼠骨髓细胞微核的影响因素，确定其在经口试验中作为阳性对照使用最佳组合。[方法]小鼠一次性经口给于CP40、80mg／kg的剂量后，分别在不同的时间、不同的部位采取骨髓，观察骨髓细胞的微核率，同时观察嗜多染红细胞（PCE）和正染红细胞（NCE）的比值。[结果]小鼠在给予40mg/kg和80mg／kg CP后的骨髓徽核率随取样时间的变化趋势是一致的。而给药组PCE与NCE比值与对照组的比较差异均无统计学意义，对骨髓细胞无明显抑制作用。但80mg／kg微核率显著高于40mg／kg剂量组．表明有一定剂量反应关系。但48h采取的骨髓的微核率与24h、30h有明显下降的趋势。[结论]环磷酰胺可用作微核试验的阳性对照物。其经口的剂量范围在40-80mg／kg，采集样本的时间应在给药后24—30h。胸骨髓是微核试验的最好材料。     

稳恒、低频交变磁场对小鼠体内细胞的诱变作用

目的;研究稳恒,低频交变磁场对小鼠骨髓嗜多染红细胞（PCE）微核率和血象分析的影响。方法：稳恒磁场强度为（40,50,60mT)和低频交变磁场强度为（10,16mT)分别作用于小鼠,每天2次,每次2h,15天后检测微核率和进行血象分析。结果：实验组小鼠微核核率较阴性对照组明显增高（P＜0．05）,较阳性对照组仍有显著性差异（P＜0．01）,而红细胞和白细胞分类无明显变化,低频交变磁场实验组白细胞数量减少。结论：当小鼠受到稳恒磁场50,60mT和低频交变磁场10,16mT作用时,使细胞微核率增加,可致其细胞行为功能改变。     

六苄基六氮杂异伍兹烷暴露小鼠骨髓细胞微核及染色体畸变研究

将SPF级昆明小鼠按体重随机分为5组,分别为0(阴性对照)、500、1 000、2 000 mg/kg六苄基六氮杂异伍兹烷(HBIW)染毒组以及30 mg/kg环磷酰胺组。采用小鼠骨髓嗜多染细胞微核试验检测嗜多染红细胞(PCE)微核率和PCE与正染红细胞(NCE)比值,采用骨髓细胞染色体畸变试验检测染色体数目及结构畸变率。结果显示,与阴性对照组相比,各剂量染毒组小鼠PCE微核率、PCE/NCE、染色体数目及结构畸变率差异均无统计学意义。提示在本实验剂量范围内,HBIW对小鼠骨髓细胞无致突变效应。     

三硝基甲苯和4-氨基-2,6-二硝基甲苯对小鼠骨髓细胞染色体畸变率和微核率的影响

观察了三硝基甲苯（TNT）10、50、100mg／kg和4-氨基-2，6-二硝基甲苯（4－A）50、100、200、40Cmg／kg剂量组对C57BL小鼠骨髓细胞染色体畸变率和嗜多染红细胞（PCE）微核率的影响。实验结果显示，TNT和4－A各剂量组小鼠骨髓细胞染色体畸变率明显增高，P<0．01而且呈剂量效应关系。相同剂量4－A诱发染色体畸变率明显低于TNT，P<0．01。小鼠骨髓PCE微核率10、50mg／kgTNT剂量组明显增高，而4－A剂量至400mg／kg其微核率的增高无统计学意义。表明三硝基甲苯进入体内并代谢转化为4－A之后，仍具有较强的体细胞诱变活性，但呈减弱趋势。     

二氧化硫吸入诱发小鼠骨髓细胞染色体畸变的效应

目的 为了了解二氧化硫（SO2）吸入对小鼠骨髓细胞染色体畸变（CA）的诱发作用。方法 以不同浓度SO2气体对小鼠熏气,随后分析小鼠骨髓细胞分裂指数和染色体畸变（CA）率和畸变细胞率。结果 SO2可诱发细胞CA率和畸变细胞率显著增高,且呈明确的剂量－反应关系。在SO2不同浓度（0、14、28、56及84ng/m^3）染毒条件下,小鼠骨髓细胞畸变细胞率（％）分别为1．81、3．00、3．58、4．26、4．86。SO2在低浓度下主要诱发染色单体型畸变,在高浓度下既可引起染色单体畸变,又可引起染色体型畸变。SO2可引起骨髓细胞分裂指数显著降低。结论 吸入SO2气体可抑制小鼠骨髓细胞分型,引起染色体畸变,SO2是染色体断裂剂和基因毒性因子。长期接触环境低浓度SO2污染,有引起接触人群体内细胞遗传物质损伤的潜在危险。     

二氧化硫吸入对小鼠肺和心组织DNA-蛋白质交联作用的影响

[目的]研究二氧化硫（SO2）吸入致小鼠肺、心组织蛋白质氧化损伤和对DNA-蛋白质交联（DPC）率的影响.[方法]分别用浓度为14、28、56mg／m^3的SO2气体对小鼠动态染毒7d（每天6h）,对照组小鼠在同样饲养条件下吸入新鲜空气。用2,4．二硝基苯肼（DNPH）比色法测定蛋白质羰基（PCO）含量,用KCl-SDS法测定DPC率。[结果]SO2各染毒浓度组与对照组相比,均可致小鼠肺、心PCO含量和DPC率升高。雌性小鼠SO2染毒浓度与肺、心PCO含量的回归方程分别为：y=0．1744x＋4．192（R^2=0．9998）,y=0．0420x＋3．896（R^2=0．9763）;雄性小鼠分别为：y=0．0441x＋4．204（R^2=0．9945）,y=0．1553x＋4．488（R^2=0．9883）,均呈现明显的剂量．效应关系。雌性小鼠SO2染毒浓度与肺、心DPC率回归方程分别为：y=0．0395x＋1．404（R^2=0．9913）,y=0．0121x＋1．614（R^2=0．9902）;雄性小鼠分别为：y=0．0132x＋1．616（R^2=0．9821）,y=0．0329x＋1．45（R^2=0．9922）,同样呈现明显的剂量-效应关系。[结论]SO2吸入可致小鼠肺、心PCO含量和DPC率呈剂量依赖性升高。随着SO2浓度的增加,对肺、心蛋白质的氧化损伤加剧,DPC率升高。吸入同浓度SO2小鼠的肺、心PCO含量和DPC率结果表明,对肺的损伤远大于心。     

Ce(SO4)2对玉米根尖细胞遗传毒性和细胞毒性的研究

[目的]研究Ce(SO4)2对玉米根尖细胞的遗传毒性和细胞毒性。[方法]用不同梯度浓度的Ce(SO4)2对玉米根尖细胞进行染毒处理，检测玉米根尖细胞的微核率和有丝分裂指数。[结果]当Ce(SO4)2≥10mg/L时，玉米根尖细胞的微核率显著上升，当Ce(SO4)2达到1000mg／L时，玉米根尖细胞的有丝分裂指数显著下降。[结论]提示一定浓度的Ce(SO4)2对玉米根尖细胞具有一定的遗传毒性和细胞毒性。     

Effect of sulfur dioxide hydrates on cell cycle, sister chromatid exchange, and micronuclei in barley

The effects of sulfur dioxide (SO(2)) hydrates exposure on cell cycle, sister chromatid exchange (SCE), and micronuclei (MN) were investigated in barley (Hordeum vulgare) roots. A mixture of sodium bisulfite and sodium sulfite (1:3), at various concentrations from 1x10(-5) to 3x10(-2)M, was used for the treatments. The results showed that the mixture induced the formation of SCE and MN in barley root cells with different effective concentrations and with different trends as treatment concentrations increased. At high concentrations of 0.5-30.0mM, SO(2) hydrates inhibited the mitotic activity and the growth of barley roots by cell cycle delay and cell death, but at 0.1mM, the chemicals slightly stimulated mitotic activity and root growth. These remarkable effects in causing DNA damage and consequent chromosome damage suggest that SO(2) is genotoxic agent and its genotoxicity may influence the mitotic activity and plant growth under SO(2) stress.     

Radioprotective properties of histamine H2 receptor antagonists: present and future prospects

Various chemical agents were examined for their radioprotective capability to provide partial protection against radiation injury over the past 50 years. However, no suitable drug has yet been introduced for routine clinical use. In the present study, the radioprotective potential of H2 receptor antagonists was examined in in vivo and in vitro conditions. For this purpose, an in vivo micronucleus assay and an in vitro metaphase analysis were used to test the effects of cimetidine, ranitidine, and famotidine on radiation-induced clastogenic effects. For micronuclei assay, BALB/c mice were irradiated in the presence or absence of drugs, and slides were prepared from bone marrow cells. The frequency of micronuclei was determined in bone marrow erythrocytes. For the in vitro assay, lymphocytes in whole peripheral blood were exposed to radiation in the presence or absence of drugs, and the frequency of chromosomal aberrations were determined. The results show that radiation produced a high number of micronuclei in polychromatic erythrocytes (PCE) and chromosomal aberrations in lymphocytes. All three drugs used in this study effectively reduced the frequency of radiation-induced micronuclei and chromosomal aberrations at various doses. Famotidine was found to be more effective than the other two drugs. From the results obtained, it can be concluded that H2-receptor antagonists reduced the clastogenic effects of radiation with a dose reduction factor (DRF) of 1.5-2 in vivo and in vitro. The way in which these drugs reduce the clastogenic effects of radiation might be via a radical scavenging mechanism.     

吸入二氧化硫对小鼠脑细胞DNA的损伤作用

目的：了解吸入二氧化硫（SO2）对小鼠脑细胞DNA的损作用。方法：用单细胞凝胶电泳技术（又称彗星试验）研究脑细胞的DNA损伤,结果：在SO2浓度为0,7,14及28mg/m^3的染毒条件下,雄性小鼠脑细胞核DNA拖尾的长度分别为8．02,23．14,46．43及53．49μm,雌小鼠则分别为7．23,12．43,20．39及54．83μm,结果表明,SO2可引起小鼠脑细胞DNA损伤,且随SO2吸入浓度的增高,DNA损伤加重,具有明确的剂量效应关系,即使在吸入低浓度SO2（7mg/m^3)的条件下,有DNA损伤的脑细胞也达98．8％,表明脑细胞对SO2的毒作用非常敏感;SO2对雌性小鼠脑细胞的DNA损伤比雄性小鼠弱,结论：即使吸入低浓度SO2也有引起哺乳类动物脑细胞DNA突变的潜在危险,从而为接触SO2工人的脑肿瘤死亡的增高的流行病学调查结果提供了科学依据。     

Inhalation studies of Mt. St. Helens volcanic ash in animals. III. Host defense mechanisms

The effects of inhalation exposure of mice or rats to 9.4 mg/m3 volcanic ash, 2.5 mg/m3 SO2, or both on host defense mechanisms were assessed. Cytologic changes in pulmonary lavage fluid included an increase in percentage polymorphonuclear leukocytes due to SO2 exposure and an increase in eosinophils due to ash. SO2 and ash also produced decreases in percentage alveolar macrophages. In the case of ash-exposed animals, this decrease was offset by an increase in lymphocytes. Total cell counts and viability were not affected by any of the exposures. Pulmonary clearance mechanisms were affected in that there were both decreased alveolar macrophage phagocytic capability following ash and ash + SO2 exposures and depressed ciliary beat frequency attributable to ash exposure. None of the inhalation exposures caused increases in susceptibility to an immediate or 24 hr postexposure aerosol challenge with Streptococcus. However, intratracheal instillation of both fine- and coarse-mode volcanic ash caused slight but significant increases in mortality due to bacterial challenge 24 hr after the instillation. The phytohemagglutinin-induced blastogenic response of splenic lymphocytes from exposed animals did not differ significantly from that of control lymphocytes, although the lipopolysaccharide-induced blastogenic response was enhanced. Ash exposure had no effect on susceptibility to murine cytomegalovirus. In summary, volcanic ash alone or in combination with SO2 had only minimal effects on certain host defense mechanisms.     

Micronuclei induced by municipal landfill leachate in mouse bone marrow cells in vivo

The induction of micronuclei (MN) in polychromatic erythrocytes (PCE) of mouse bone marrow by municipal landfill leachate was studied in vivo. Results showed that mouse exposure via drinking water containing various concentrations of leachate caused a significant increase of MN frequencies in a concentration (Chemical oxygen demand measured with potassium dichromate oxidation, COD(Cr))-dependent manner. MN induction in female and male mice was different at higher concentrations. This implies that leachate is a genotoxic agent in mammalian cells and that exposure to leachate in an aquatic environment may pose a potential genotoxic risk to human beings.     

二氧化硫吸入对大鼠血红细胞的氧化损伤作用

目的 为了研究低浓度和二氧化硫（SO2）毒理作用的机理。方法 测定SO2（14mg/m^3）吸入对大鼠血红细胞抗氧化酶活性和脂质过氧化水平的影响。结果 SO2吸入可引起超氧化歧化酶（Cu、Zn－SOD）活性降低、谷胱甘肽过氧化物酶（GSH－Px）活性升高、过氧化氢酶（CAT）活性无明显改变,以及红细胞脂质过氧化水平显著升高。结论 SO2通过产生活性自由基引起脂质及其它生物大分子的氧化损伤,可能是低浓度SO2毒理作用的主要机制。     

TK6和WTK1细胞体外微核试验比较研究

目的：比较5种诱变剂诱导人类淋巴母细胞TK6和WTK1的微核反应。方法：用人的类淋巴母细胞TK6和WTK1进行体外微核试验，评价5种诱变剂的染色体损伤效应。结果：5种受试物均可诱导两种细胞微核率显著升高，但在大多数剂量和采样时间，受试物诱导的TK6细胞微核率均不同程度地高于WTK1细胞微核率。结论：TK6细胞对受试物诱导的染色体损伤更为敏感。     

Oxidative damage of sulfur dioxide inhalation on lungs and hearts of mice

Effects of sulfur dioxide (SO2) on concentrations of thiobarbituric acid-reactive substances (TBARS) and reduced glutathione (GSH), activities of Cu,Zn-superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were investigated in lungs and hearts of Kunming albino mice of both sexes. The mice of SO2 groups were exposed to various concentrations (22, 56, and 112 mg/m3) of SO2 in separate exposure chambers for 6 h/day for 7 days, whereas control groups were exposed to filtered air under otherwise the same conditions. Our results show that SO2 caused lipid peroxidation and changes of antioxidative status in both lungs and hearts of mice. Exposure to SO2 at all concentrations tested caused a significant increase of TBARS and a significant decrease in GSH content in lungs and hearts of mice, with the exception of GSH content in the hearts of female mice. For lungs, SO2 at low concentrations significantly increased SOD and GPx activities, whereas at high concentrations it significantly decreased these same activities in mice of both sexes. For hearts, SO2 at all tested concentrations significantly decreased activities of SOD from mice of both sexes, as well as that of GPx from male mice, but the decrease of GPx activities in hearts from female mice was statistically insignificant. SO2 inhalation tended to decrease activities of CAT in lungs and hearts from mice of both sexes, whereas only the decrease of CAT activities caused by SO2 in lungs from male mice was statistically significant, at 112 mg/m3. The results also show a gender difference in oxidative stress and antioxidation status caused by SO2 exposure. These results lead us to conclude that SO2 exposure can cause oxidative damage to lungs and hearts of mice, and SO2 is toxic not only to the respiratory system, but to the heart as well. Additional work is required to understand the toxicological role of SO2 on many or even all mammalian organs.