二乙基亚硝胺(DEN)诱发λ/lacZ转基因小鼠微核和基因突变实验研究

目的　应用λlacZ转基因小鼠检测二乙基亚硝胺(DEN)诱发体内遗传毒性。方法　小鼠腹腔注射DEN(2. 5mg kg) ,每周1次,连续4周。染毒4 8小时后检测外周血微核细胞率。末次染毒7天后处死动物,提取组织DNA ,通过体外包装反应获得并测定肝脏、肺脏、膀胱lacZ基因突变频率。结果　DEN诱发微核率与对照组无显著性差异,肝脏组织lacZ基因突变(MF)为2 6 8 .4×10 - 6 ,是对照组的6 .13倍,肺脏MF也明显高于对照,是其3 6 6倍,而膀胱组织MF则与对照无显著性差异。结论　肝脏、肺脏均是DEN致突变的靶器官,但对其敏感度并不相同。     

人类淋巴母细胞TK6检测环磷酰胺诱发微核及TK基因突变的体外实验研究

目的 建立TK6细胞检测环境诱变剂诱发微核及TK基因突变的实验方法。方法 用诱变剂环磷酰胺(CP)体外染毒TK6细胞4h后检测细胞毒性,微核及kt位点突变频率。结果 CP处理导致TK6细胞的相对存活率下降,细胞微核率及TK基因突变频率明显上升,并均有剂量——反应关系。最高浓度组(4．0μg／ml)的细胞微核率及TK基因突变频率分别是对照组的8、8和15．7倍。CP诱发tk位点两种不同表型的突变细胞集落,即正常生长突变体集落及缓慢生长突变体集落,并以后者为主。结论 CP可以诱发TK6细胞微核及TK基因突变,揭示CP可能是一种断裂剂。TK6细胞可用于评估环境化学物细胞水平遗传改变及TK基因突变。     

铁路危险品货运站空气颗粒污染物有机提取物的小鼠外周血网织红细胞微核试验

目的探讨铁路危险品货运站空气颗粒污染物对小鼠外周血网织红细胞微核的诱导作用.方法选用雄性BALB/c小鼠随机分为实验组和对照组,空气颗粒污染物的丙酮提取物按20、40、80、160 mg/kg的剂量,以腹腔注射方式一次性染毒.同时进行低剂量(10 mg/kg)腹腔注射重复式染毒,每天1次共5天,于染毒后24、48、72 h采集尾血进行网织红细胞微核分析.结果外周血网织红细胞微核率呈现出良好的时间-反应关系,微核的高峰出现在染毒后48 h,此时各剂量组微核率均高于对照组.低剂量重复染毒试验结果表明,在24～72 h内网织红细胞微核率始终处于较高水平,与对照组相比差异有显著性(P＜0.05).结论铁路危险品货运站空气颗粒污染物对雄性小鼠外周血网织红细胞微核具有明显的诱导作用.     

甲醛致胎鼠肝微核率及染色体畸变的研究

目的探讨甲醛致胎鼠肝微核率与染色体畸变。方法随机将妊娠小鼠(孕13天)分为5组:腹腔注射甲醛(0.00、0.20、2.00、20.00mg/kg)染毒组、环磷酰胺(30mg/kg)阳性对照组,实验至妊娠第14天即染毒后18小时脱颈椎处死孕鼠,剥离两侧子宫,每侧各取一胎鼠,断头放出外周血,取胎肝,采用胎肝微核试验和胎肝染色体畸变试验,检测胎肝血微核率和染色体畸变率。结果2.00、20.00mg/kg甲醛染毒组胎肝微核率及胎肝染色体畸变率与阴性对照组比较差异有显著性(P<0.01);染色体畸变主要表现为染色体断裂、多倍体等畸形。结论甲醛可致胎鼠肝微核率与染色体畸变。     

串场河水诱发蝌蚪血红细胞微核的研究

本文通过测定蝌蚪血红细胞微核率进行串场河河水致变效应的研究。实验中用蝌蚪作实验动物，在串场河不同地段采来的水样中染毒一周，测定其血红细胞微核率。实验结果表明，串场河水能诱发蝌蚪血红细胞微核率升高，与饮用水相比差异极显著。     

氯化镍染毒对小鼠外周血网织红细胞微核形成的影响

目的研究氯化镍(NiCl2)诱导小鼠外周血网织红细胞微核形成的作用.方法将30只健康的成年雄性NIH小鼠随机分为6组,设生理盐水对照组、秋水仙素阳性对照组(剂量为0.75 mg/kg)、环磷酰胺阳性对照组(剂量为40.0mg/kg)和NiCl2染毒组(剂量分别为5.0、10.0、20.0 mg/kg),分2次腹腔注射染毒,间隔24 h,每次按0.1 ml/10 g体重腹腔注射.采用转铁蛋白受体荧光抗体和碘化丙碇染色,以疟原虫感染小鼠外周血红细胞为微核生物模型,调校流式细胞仪,检测秋水仙素、环磷酰胺和0、5.0、10.0、20.0 mg/kg NiCl2染毒后小鼠外周血含微核网织红细胞率的变化.结果秋水仙素和环磷酰胺染毒小鼠的外周血含微核网织红细胞率均明显高于对照组小鼠(P＜0.01),但不同剂量NiCl2染毒小鼠外周血含微核网织红细胞率均未见明显升高(P＞0.05).结论该研究条件下未观察到氯化镍有明显的诱导小鼠外周血网织红细胞微核形成的作用.     

长期低剂量接触2,3,7,8-四氯二苯并-p-二噁英对大鼠骨髓细胞微核和精子形态的影响

目的了解长期低剂量接触2,3,7,8-四氯二苯并-p-二噁英(TCDD)对雄性SD大鼠骨髓细胞微核和精子形态的影响。方法将1月龄SD大鼠随机分为4组,分别为阴性对照组(给予玉米油)和3个TCDD染毒组(日染毒剂量为2、10、50ng/kg)。13周后,另设微核阳性对照组(环磷酰胺,日染毒剂量为60mg/kg,连续3d)观察骨髓嗜多染红细胞微核率和精子畸形率。结果长期低剂量接触TCDD导致大鼠骨髓细胞微核率增加,精子畸形率增高。阴性对照组、2、10、50ng/kg染毒组、阳性对照组微核率分别为9.0‰,13.0‰,21.2‰,24.4‰和87.4‰,10、50ng/kg组微核率均高于阴性对照组(均P0.01);对照组、2、10、50ng/kg组精子畸形率分别为10.4‰,35.0‰,49.8‰,47.0‰,各染毒组畸形率均高于对照组(均P0.01),畸形以颈折叠为主。结论长期低剂量接触TCDD对哺乳动物体细胞和雄性生殖细胞具有致突变性,且生殖细胞对TCDD的毒性更敏感。     

甲醛和二甲苯联合染毒对小鼠骨髓细胞遗传毒性研究

目的探讨甲醛和二甲苯联合染毒对小鼠骨髓细胞的遗传毒性作用。方法将78只健康清洁级昆明小鼠,按体重随机分为13组,分别为低剂量甲醛染毒组(5 mg/kg)、中剂量甲醛染毒组(10 mg/kg)、高剂量甲醛染毒组(20mg/kg)以及生理盐水(0.01 ml/g)对照组;低剂量二甲苯染毒组(50 mg/kg)、中剂量二甲苯染毒组(100 mg/kg)、高剂量二甲苯染毒组(150 mg/kg)以及花生油(0.01 ml/g)对照组;低剂量联合染毒组(2.5 mg/kg甲醛+25 mg/kg二甲苯)、中剂量联合染毒组(5 mg/kg甲醛+50 mg/kg二甲苯)、高剂量联合染毒组(10 mg/kg甲醛+75 mg/kg二甲苯)以及生理盐水+花生油(体积比1∶1)对照组;环磷酰胺(40 mg/kg)作为微核试验阳性对照组。每组6只,雌雄各半。采用腹腔注射方式染毒,每天1次,连续7 d。染毒结束次日处死小鼠,采用微核试验和彗星试验检测骨髓细胞的遗传毒性作用。结果甲醛、二甲苯单独或联合染毒均可引起小鼠骨髓细胞微核率增高(P<0.05),且微核率随着染毒剂量的增加而上升。甲醛与二甲苯联合染毒组微核率高于各自单独染毒组,在高剂量联合染毒组尤其明显(P<0.05)。甲醛、二甲苯单独或联合染毒均可使小鼠骨髓彗星细胞尾部DNA含量及尾矩增加,且高剂量组尤其明显(P<0.05);二者在较低剂量联合染毒时便致彗星细胞尾部DNA含量及尾矩较甲醛和二甲苯单独染毒组有所增加(P<0.05);且随着染毒剂量的升高,联合染毒毒性作用明显上升。结论甲醛、二甲苯染毒对小鼠骨髓细胞具有遗传毒性作用,二者联合染毒可能存在协同毒性效应。     

口腔清新剂急性毒性及诱变性

[目的 ]口腔清新剂是以天然中草药为原料制成的口腔保健制品。为评价其安全性 ,作了急性毒性试验和微核试验。[方法 ]实验按GB7919 87标准进行。实验动物均由沈阳医学院实验动物中心提供。急性经口毒性试验按Horn氏法。用昆明种健康小鼠 ,雌雄各半 ,体重 2 0～ 2 2g ,共 40只。皮肤刺激试验用新西兰兔 4只 ,体重 2kg。实验前一天去毛 ,范围 3× 3cm2 。用皮肤无损伤的兔染毒 ,观察皮肤反应并计算刺激反应积分。眼刺激试验用新西兰兔 ,体重 2kg ,共计 4只。用原液滴眼。记录观察冲洗后 6h、2 4h、48h眼部变化和第 4天、第 7天恢复情况。骨髓嗜多染红细胞微核试验用昆明种健康小鼠 2 5只 ,随机分成 5组 ,采用二次灌胃染毒 ,相隔 2 4h ,于第二次染毒6h后颈椎脱臼处死小鼠 ,取骨髓制片 ,镜检 ,计算微核率。 [结果 ]雌雄小鼠经口LD50 均大于 5 0 0 0mg/kg。原液对家兔皮肤无刺激性 ,对家兔眼也无刺激性。实验组与阴性对照组间微核检出率相比无显著性差异。环磷酰胺阳性组与实验组相比 ,则有显著性差异。 [结论 ]口腔清新剂小鼠急性经口毒性属实际无毒类。对皮肤和眼无刺激性。微核试验阴性     

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。     

Effect of alpha-tocopherol on hepatocarcinogenesis in transforming growth factor-alpha (TGF-alpha) transgenic mice treated with diethylnitrosamine.

To examine the potentially chemopreventive effects of alpha-tocopherol on hepatocarcinogenesis, we fed the transgenic mice line MT42, which overexpresses transforming growth factor-alpha (TGF-alpha) and which has been established as having a high incidence of liver tumor, with different concentrations of alpha-tocopherol and examined the hepatic tumorigenesis of these mice. At 3 weeks of age, MT42 male mice received a single intraperitoneal injection of diethylnitrosamine (DEN), 5 mg/kg body weight, to initiate the formation of liver tumors. The mice were divided into three groups: group A, control diet (20 mg/kg of alpha-tocopherylacetate); group B, deficient diet (less than 1 mg/kg); group C, supplemented diet (500 mg/kg). Neoplastic change was determined at 40 weeks of age. The incidence of adenomas (p < 0.05), the maximum tumor size (p < 0.01), the mean relative liver weight (p < 0.01), and the proliferating cell nuclear antigen (PCNA) labeling indices of the non-tumor sites (p < 0.01) of group B were significantly higher than those of group C. No toxic effects of alpha-tocopherol were found. Alpha-tocopherol-deficient diet accelerated the hepatocarcinogenesis of TGF-alpha transgenic mice treated with DEN. At best, these data demonstrate that alpha-tocopherol-deficiency is not beneficial for prevention of hepatocarcinogenesis in this model. Alpha-tocopherol may be useful for the chemoprevention for liver cancer.     

Ethanol ingestion combined with lowered carbohydrate intake enhances the initiation of diethylnitrosamine liver carcinogenesis in rats.

The effect of ethanol on the initiation of diethylnitrosamine- (DEN) induced liver carcinogenesis was investigated in rats. In the first experiment, eight-week-old male Wistar rats were maintained on four liquid diets: a basal diet (Group 1), a low-carbohydrate (low-CHO) diet (Group 2), a basal diet+ethanol (Group 3), or a low-CHO diet+ethanol (Group 4). After three weeks on these diets, 50 mg/kg of DEN was injected intraperitoneally. The plasma glutamic-oxaloacetic transaminase activity in Group 4 was higher 24 hours after DEN administration than in Groups 1 and 3. The plasma glutamic-pyruvic transaminase activity in Groups 3 and 4 was higher than in Groups 1 and 2. The number of gamma-glutamyltranspeptidase-positive foci per unit liver area 41 weeks after DEN administration was higher in Group 4 than in Group 1. The area of gamma-glutamyltranspeptidase-positive foci was greater in Groups 2 and 4 than in Group 1. In the second experiment, Groups 1 and 4 were given DEN orally (25 or 75 mg/kg). Plasma glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase activities 24 hours after DEN administration were significantly higher in Group 4 than in Group 1, but only when the dose of DEN was 75 mg/kg. In contrast, the number and area of placental glutathione S-transferase-positive foci per unit liver area were greater in Group 4 than in Group 1 only after 25 mg/kg of DEN. Thus the severity of hepatotoxicity and the incidence of precancerous liver lesions were not necessarily correlated. These findings together indicate that a combination of ethanol and a low-CHO diet enhances DEN-induced liver carcinogenesis in rats by increasing the bioactivation of DEN in the liver.     

桦褐孔菌多糖对二乙基亚硝胺致肝脏损伤的保护作用

[目的]研究桦褐孔菌多糖（inonotus obliquus polysaccharide）对二乙基亚硝胺（DEN）致肝脏损伤的保护作用。[方法]将50只小鼠随机分为5组：阴性对照组（蒸馏水）,DEN组（20 mg/kg）,桦褐孔菌多糖高（600 mg/kg）、中（300 mg/kg）、低（150 mg/kg）剂量组。阴性对照组及桦褐孔菌3个剂量组每日灌胃,同时DEN组和桦褐孔菌3个剂量组隔日腹腔注射DEN,持续5周。采用HE染色法观察动物肝细胞核分裂相及枯否细胞数;采用酶动力学法测定肝组织匀浆上清液中谷胱甘肽-S-转移酶（GSTs）和微量丙二醛（MDA）含量;采用酶联免疫吸附法（ELISA）检测肝组织匀浆上清液中肿瘤坏死因子α（TNF-α）含量。[结果]DEN组肝组织中核分裂相和枯否细胞数明显多于阴性对照组（P〈0.01）,桦褐孔菌多糖高剂量组肝组织中核分裂相和枯否细胞数显著低于DEN组（P〈0.05）。DEN组肝组织中GSTs活性明显低于阴性对照组（P〈0.05）,MDA和TNF-α含量明显高于阴性对照组（P〈0.01或P〈0.05）。桦褐孔菌多糖高剂量组和中剂量组肝组织中GSTs活性明显高于DEN组（P〈0.01）,3个剂量组肝组织中MDA含量均显著低于DEN组（P〈0.01或P〈0.05）,只有高剂量组肝组织中TNF-α含量明显低于DEN组（P〈0.05）。[结论]桦褐孔菌多糖对DEN致肝脏损伤有一定的保护作用。     

Transgenic alfalfa that accumulates piceid (trans-resveratrol-3-O-beta-D-glucopyranoside) requires the presence of beta-glucosidase to inhibit the formation of aberrant crypt foci in the colon of CF-1 mice

Plants have been genetically enhanced to produce a number of products for agricultural, industrial and pharmaceutical purposes. This technology could potentially be applied to providing chemoprevention strategies to the general population. Resveratrol (3,5,4'-trihydroxystilbene) is a compound that has been shown to have protective activity against a number of cancers and could be an ideal candidate for such an application. Alfalfa that was genetically modified to express resveratrol-synthase was used as a model in applying biotechnological approaches to cancer prevention. The transgenic alfalfa, which accumulates resveratrol as a glucoside (piceid = trans-resveratrol-3-O-Beta-D-glucopyranoside) (152 +/- 17.5 microg piceid/g dry weight), was incorporated into a standard mouse diet at 20% of the diet by weight and fed for 5 wk to 6-wk-old, female CF-1 mice (N = 17-30) that were injected with a single dose of azoxymethane (5 mg/kg body weight). While the addition of resveratrol-aglycone (20 mg/kg diet) to the basal diet reduced the number of aberrant crypt foci/mouse, the transgenic alfalfa did not inhibit the number, size, or multiplicity of aberrant crypt foci in the colon of the CF-1 mice relative to control alfalfa which does not accumulate resveratrol-glucoside. However, diets containing transgenic alfalfa with an exogenous Beta-glucosidase (860 U/kg diet) did significantly inhibit the number of aberrant crypt foci in the distal 2 cm of the colon of the mice relative to mice fed diets containing the transgenic alfalfa without the enzyme (P < 0.05; Fisher's Combination of p-values). The Beta-glucosidase alone appeared to have no effect on the inhibition of aberrant crypt foci. These results suggest that piceid in transgenic piceid-accumulating alfalfa was not bioavailable.     

微囊藻毒素LR对SD大鼠的短期毒效应研究

目的：研究和探讨微囊藻毒素（MCLR）对动物的短期毒效应作用。方法：SD大鼠经腹腔注射不同剂量的MCLR,分别于注射的1、7d和停药后第7天（即第14天）采目力大鼠的血清和肝、肾、心等组织标本,经酶学及病理学检验,观察其损伤效应。结果：122цg/kg剂量组,注射后24h可观察到大鼠心肌细胞肌浆溶解,核变性固缩,肌原纤维局部坏死;血清中天冬氨酸转氨酶(AST)、乳酸脱氢酶（LDH）和磷酸肌酸激酶（CPK）与其他组相比显著升高;肾细胞变性,血清中肌酐（BCr）和尿素氮（BUN）亦显著升高;同时肝细胞片状出血、坏死,注射剂量为50цg/kg和25цg/kg时,仍出现肝细胞重度和轻度颗粒变性。血清中丙氨酸转氨酶（ALT）、碱性磷酸酶（LDH）和AST显著上升。对照组大鼠的肝、肾、心等脏器均正常。结论：MCLR可引起SD大鼠肝、肾、心等脏器的短期毒效应,且随着剂量的增加,损伤效应加重。     

吡非尼酮抗百草枯中毒小鼠肺纤维化的研究

目的 探讨吡非尼酮(PF)对百草枯(PQ)中毒小鼠肺纤维化的治疗作用,为临床治疗提供理论依据.方法 雄性ICR小鼠90只,随机分为正常对照组、PQ组、地塞米松组、25、50和100 mg/kgPF组,每组15只.正常对照组小鼠一次性空腹灌胃给予生理盐水,2 h后给予质量分数为1%羧甲基纤维素(CMC)灌胃,再每天定时空腹灌胃同等量CMC;PQ组、地塞米松组及各PF剂量组小鼠给予PQ100mg/kg一次性灌胃染毒,灌胃后2 h,再每天定时PQ组给予0.02ml/10 gCMC灌肠,PF组给予PF(25、50、100 mg/kg)和地塞米松(0.02 ml/10 g)灌胃,每天1次,共49 d.计算肺系数,HE染色,光学显微镜下观察肺组织病理改变;测定肺组织羟脯氨酸(HYP)含量,转化生长因子(TGF-β1)的mRNA表达水平、蛋白表达水平,支气管肺泡灌洗液(BALF)中的TGF-β1蛋白含量.结果 PQ组3 d生存率为53.33%,25、50、100 mg/kg PF组3 d生存率分别为46.67%、73.33%、86.67%,地塞米松组3 d生存率为80%,地塞米松组、50、100 mg/kg PF组3 d生存率明显高于PQ组和25 mg/kg PF组,差异有统计学意义(P＜0.05).25、50及100mg/kg PF组小鼠肺系数均明显低于PQ组,差异有统计学意义(P＜0.05).地塞米松组肺组织中HYP含量为(50.95±11.65)mg/g,25、50、100mg/kg PF组HYP含量分别为(44.52±9.48)、(43.27±6.01)、(40.82±5.90)mg/g,较PQ组[(74.27±3.68)mg/g]明显下降,差异均有统计学意义(P＜0.01).地塞米松组BALF中TGF-β1蛋白含量为(22.03±7.27)mg/ml,25、50、100 mg/kg PF组TGF-β1蛋白含量分别为(55.33±17.50)、(27.75±5.84)、(21.31±6.82)mg/ml,与PQ组[(52.52±15.51)mg/ml]相比,明显降低,差异有统计学意义(P＜0.01);100 mg/kg PF组肺组织TGF-β1mRNA表达水平与PQ组相比,明显下降,差异有统计学意义(P＜0.01)与PQ组比较,地塞米松组,50、100mg/kgPF组肺组织中TGF-β1蛋白表达下降,差异有统计学意义(P＜0.01).结论 PF可以减少百草枯中毒小鼠肺组织胶原沉积,减轻肺部纤维化程度.

Abstract：

Objective To study the curative effects of pirfenidone (PF)on pulmonary fibrosis induced by paraquat (PQ) in mice and to provide the theoretical basis for clinical treatment. Methods Ninety adult healthy male ICR mice were randomly divided into six groups: control group, PQ group , 2 mg/kg Dexamethasone group, 25 mg/kg PF group, 50 mg/kg PF group and 100 mg/kg PF group, there were 15 mice in each group. The corresponding volume of normal saline was given to the each mouse in control group according to the weight, after 2 h 0.1% CMC was given to the each mouse of control group one time by intragastric administration, then the CMC was administrated at regular time until sacrifice. All mice for other 5 groups were exposed to 100 mg/kg PQ by intragastric administration. At 2 h after exposure to PQ, 0.02 ml/10 g dexamethasone and 25、50、100 mg/kg PF were given to mice for dexamethasone group and for 3 PF groups by intragastric administration each day for 49 days, respectively. The lung coefficient was calculated and pathological changes of lung tissue were observed by HE staining for each mouse. The hydroxyproline (HYP)level in lung tissue was measured for each mouse. The mRNA level of and the protein level of TGF-β1 in lungtissue for each mouse were determined, and the protein level of TGF-β1 in the bronchus-alveolus lavage fluid (BALF) of each mouse was detected. Results The survival rates on the 3rd day in PQ group, 3 PF groups and dexamethasone group were 53.33%, 46.67%, 73.33%, 86.67% and 80%, respectively. The survival rates on the 3rd day in dexamethasone group, 50 mg/kg and 100 mg/kg PF groups were significantly higher than those of PQ group and 25 mg/kg PF group (P＜0.05). The lung coefficients of 3 PF groups were significantly lower than that of the PQ group (P＜0.05). The lung tissue HYP levels of dexamethasone group and 3 PF groups were 50.95±11.65, 44.52±9.48, 43.27±6.01 and 40.82±5.90 mg/g respectively, which were significantly lower than that (74.27±3.68) of PQ group(P＜0.01 ). The TGF-β1 protein levels of BALF in dexamethasone group, 50 and 100 mg/kg PF groups were 22.03±7.27, 27.75±5.84 and 21.31 ±6.82 ng/ml respectively, which were significantly lower than that(52.52±15.51 ) ng/mlof PQ group(P＜0.01 ). The expression level of TGF-β1 mRNA in 100 mg/kg PF group decreased significantly, as compared with PQ group (P＜0.01). Conclusion PF could reduce the collagen deposition and pulmonary fibrosis induced by PQ in mice lungs.     

地塞米松诱导裸鼠宫颈癌移植瘤凋亡的实验研究

目的:探讨地塞米松对宫颈癌Hela细胞裸鼠移植瘤生长及凋亡的作用。方法:BALB/C裸鼠皮下接种宫颈癌Hela细胞,腹腔内注射不同剂量地塞米松15~250mg/kg,测量肿瘤体积观察肿瘤生长情况,用透射电镜及原位细胞凋亡检测(TUNEL)的方法对肿瘤细胞的凋亡进行检测。结果:不同剂量地塞米松体内注射均可抑制宫颈癌Hela细胞裸鼠移植瘤的生长,并能诱导肿瘤细胞凋亡,与对照组相比肿瘤生长速度减慢,体积明显缩小(P<0·001),凋亡小体明显增多;不同剂量地塞米松对肿瘤生长的影响有差异,当剂量<62·5mg/kg时,疗效随剂量增加而增加,凋亡小体逐渐增多,肿瘤生长更加缓慢,各组间有明显差异(P<0·001);剂量为62·5~125mg/kg时,肿瘤生长及凋亡发生与剂量无明显的关系;当剂量>125mg/kg时,疗效随剂量增加而降低,凋亡小体逐渐减少,肿瘤生长速度加快,各组间有明显差异(P<0·001)。结论:地塞米松体内能诱导裸鼠宫颈癌移植瘤凋亡发生,显著抑制肿瘤生长,并存在一定程度的剂量依赖效应。     

Expression of the insecticidal bean alpha-amylase inhibitor transgene has minimal detrimental effect on the nutritional value of peas fed to rats at 30% of the diet.

The effect of expression of bean alpha-amylase inhibitor (alpha-AI) transgene on the nutritional value of peas has been evaluated by pair-feeding rats diets containing transgenic or parent peas at 300 and 650 g/kg, respectively, and at 150 g protein/kg diet, supplemented with essential amino acids to target requirements. The results were also compared with the effects of diets containing lactalbumin with or without 0.9 or 2.0 mg bean alpha-AI, levels equivalent to those in transgenic pea diets. When 300 and 650 g peas/kg diet were fed, the daily intake of alpha-AI was 11.5 or 26.3 mg alpha-AI, respectively. At the 300 g/kg level, the nutritional value of the transgenic and parent line peas was not significantly different. The weight gain and tissue weights of rats fed either of the two pea diets were not significantly different from each other or from those of rats given the lactalbumin diet even when this was supplemented with 0.9 g alpha-AI/kg. The digestibilities of protein and dry matter of the pea diets were slightly but significantly lower than those of the lactalbumin diet, probably due to the presence of naturally occurring antinutrients in peas. The nutritional value of diets containing peas at the higher (650 g) inclusion level was less than that of the lactalbumin diet. However, the differences between transgenic and parent pea lines were small, possibly because neither the purified recombinant alpha-AI nor that in transgenic peas inhibited starch digestion in the rat small intestine in vivo to the same extent as did bean alpha-AI. This was the case even though both forms of alpha-AI equally inhibited alpha-amylase in vitro. Thus, this short-term study indicated that transgenic peas expressing bean alpha-AI gene could be used in rat diets at 300 g/kg level without major harmful effects on their growth, metabolism and health, raising the possibility that transgenic peas may also be used at this level in the diet of farm animals.     

Risk assessment of microcystin in dietary Aphanizomenon flos-aquae.

Aphanizomenon flos-aquae, a cyanobacterium that is marketed as a health food supplement, is harvested from natural blooms in Klamath Lake (Oregon) that are occasionally contaminated by Microcystis spp. Regulatory agencies in several countries are developing regulations to control the amount of microcystin in drinking water and other products, including products produced from A. flos-aquae. Regulation of microcystin (MC), a toxin produced by Microcystis spp. that is potentially present in natural culture of A. flos-aquae, should be based on studies in which a test species is exposed to the natural mixture of these cyanobacteria. A 1984 feeding trial to determine the effects of high dietary levels of A. flos-aquae on reproduction and development of mice is reanalyzed in light of recent analyses for microcystin-LR (MCLR) in the diets of those mice. Young adult mice consuming up to 333 microg MCLR/kg body weight (bw)/day exhibited no adverse effects on growth and reproduction, fetal development, and survival and organ weights of neonates. Based on a NOAEL of 333 microg MCLR/kg bw/day, a safety factor of 1000, consumption of 2 g/day of A. flos-aquae by a 60-kg adult, the safe level of MCLR as a contaminant of A. flos-aquae products is calculated to be 10.0 microg MCLR/g.