中华猕猴桃的防癌作用(三)在模拟人胃液中对N-亚硝酰胺合成的阻断作用——Ames试验

本文用Ames试验的方法研究了中华猕猴桃汁对N-亚硝酰胺体外合成的阻断作用。 在模拟人胃液的条件下,亚硝酸钠和甲基硝基胍能反应生成N-甲基-N′-硝基-N亚硝基胍,在Ames氏平皿掺入试验中引起鼠伤寒沙门氏菌TA100菌株的突变反应,有明显的剂量反应关系。当亚硝酸钠浓度为50mM,甲基硝基胍为100mM时,突变菌落数高达4327个/皿,为自发回变的19.94倍。中华猕猴桃汁能阻断N-甲基-N′-硝基-N-亚硝基胍合成,抑制突变反应。在亚硝酸钠浓度为22.2mM,甲基硝基胍为44.4mM时,猕猴桃汁能完全阻断N-甲基-N′-硝基-N-亚硝基胍的合成,致突变反应为阴性。而不加猕猴桃汁的同浓度反应体系引起的突变反应为自发回变的12.59倍。桃汁组低于此浓度的反应体系结果皆是阴性,而对高于此浓度的反应体系,猕猴桃汁不能完全阻断N-甲基-N′-硝基-N-亚硝基胍合成,但能明显抑制突变反应。对中等浓度的反应体系,与桃汁含量相同的抗坏血酸溶液亦能部分阻断N-甲基-N′-硝基-N-亚硝基胍的合成,但作用低于猕猴桃汁。实验结果证明猕猴桃汁阻断N-甲基-N′-硝基-N-亚硝基胍体外合成的作用明显优于同浓度抗坏血酸溶液。 在相同实验条件下,单独的亚硝酸钠或甲基硝基胍均无致突变作用。经薄层层析方法定性分析,反应生成物是N-甲基-N′-硝基-N-亚硝基胍。     

中华猕猴桃的防癌作用 (五)阻断大鼠和健康人体内N-亚硝基脯氨酸的合成

本文报导中华猕猴桃对体内N-2硝基脯氨酸(NPRO)合成的阻断效果。研究对象为15只雄性Wistar大鼠和10名男性健康志愿者。用自身对照分期观察。大鼠实验表明,中华猕猴桃汁可阻断体内NPRO合成(阻断率59.6％),且效果优于同浓度维生素C溶液,志愿者食入150g含75mg维生素C的中华猕猴桃可完全阻断服300mgNaNO_3和500mg脯氨酸后体内的NPRO合成,而75mg维生素C仅部分阻断。     

中华猕猴桃汁阻断胃癌高发区人群的内源性N-亚硝基化合物合成

本文以空腹胃液中挥发性亚硝胺(VNA)和24小时尿N-亚硝基脯氨酸(NPRO)排出量为指标,观察中华猕猴桃汁(简称桃汁)阻断胃癌高发区人群内源性N-亚硝基化合物(NOC)合成的阻断作用。受试者服用30ml桃汁后,空腹胃液中VNA总量由平均2.08±1.06μg/L显著下降至0.42±0.43μg/L(P<0.01),阻断率为79.8％。在NPRO试验中,受试验者摄入300mg脯氨酸后,尿NPRO排出量由本底的3.3±1.2μg/d显著升高至9.4±4.7μg/d(P<0.001)。与脯氨酸同时服用30ml桃汁后,NPRO排出量显著降低至本底水平(2.9±1.9μg/d,P<0.001)。上述阻断作用在胃粘膜病变程度不同的三组人群间未见显著性差别(P>0.1)。本研究证实,中华猕猴桃汁能有效地阻断胃癌高危人群内源性NOC合成。     

中华猕猴桃的防癌作用——一、中华猕猴桃汁阻断N-亚硝基吗啉合成

我国特产中华猕猴桃汁在模拟胃液的条件下,能阻断N-亚硝基吗啉的形成。在37℃,pH3.13-3.28,吗啉及亚硝酸钠浓度各为2.0mM,经0.5、1.0及2.0小时,其阻断率分别为98.54％,96.43％及97.99％;此结果优于柠檬汁,后者阻断率分别为84.55％,34.79％及37.43％;并优于含同样量的抗坏血酸溶液,其结果分别为97.56％、89.48％及65.62％。将猕猴桃汁中抗坏血酸经酶氧化后,不同时间阻断率仍分别高达90.24％、88.47％及79.84％;氧化后的柠檬汁阻断率分别为65.04％、10.13％及50.58％。抗坏血酸溶液氧化后,保温2小时的阻断率为22.08％。 用高压液相色谱测猕猴桃浓缩计中还原型抗坏血酸,其量为264mg/100ml,柠檬汁中含量为37.0mm/100ml,其范围分别为215.4至384.6mg/100ml及21.2至67.5mg/100ml。     

大蒜对氨基比林与亚硝酸钠在大鼠体内所致毒性的预防作用

给Wistar大鼠用氨基比林、亚硝酸钠均以30mg/kg体重的剂量灌胃。实验组于普通饲料中添加10％的生大蒜,阳性对照组饲以普通饲料。对两组大鼠平均每只给予氨基比林和亚硝酸钠的总量分别为171.9mg和167.7mg。实验组在35天实验期中全部存活(12/12),阳性对照组有1只死亡(1/10),2只于濒死时被处死(2/10)。前者血红蛋白含量高于后者(P<0.05),而血清转氨酶活性低于后者(P<0.01),病理检查发现肝脏病变发生率前者为67％(8/12),后者为100％(10/10),大蒜组动物肝脏病变程度显著较阳性对照组为轻,后者除肝脏病变外尚有肺及肾的出血现象。本研究证明,大蒜能阻断氨基比林和亚硝酸钠在大鼠体内形成二甲基亚硝胺,并对其所致的毒害有明显的预防作用。     

中华猕猴桃的防癌作用——(七)阻断慢性萎缩性胃炎病人体内N-亚硝基脯氨酸合成

本文报导了中华猕猴桃汁阻断慢性萎缩性胃炎(CAG)病人体内N-亚硝基脯氨酸(NPRO)合成的作用。在11名CAG病人的自身对照研究中,病人食入300mg NaNO_3和500mg脯氨酸后,尿中NPRO从本底值26.3nmol升至63.9nmol;同时服4.1ml浓缩猕猴桃汁后,多数人尿中NPRO明显下降,阻断率达94.4％。此外,有2人体内NPRO合成水平很高,提示可能有较高的癌变危险性。     

中华猕猴桃的防癌作用 (四)浓缩猕猴桃汁阻断N-亚硝酰胺的体内合成——大鼠胚胎毒性实验

在妊娠第7、8、9天经口给孕鼠不同剂量的前体物亚硝酸钠(分别为0.125、0.25、0.50、1.00和2.00mmol/kgBW)和乙基脲(剂量是亚硝酸钠的二倍),同时给浓缩猕猴桃汁或4％淀粉液。不给猕猴桃汁的各组随前体物剂量增大,活胎率下降,吸收胎率逐渐增加,分别为5.21％,43.66％,71.70％,85.80％和100％。最高剂量组胚胎全部死亡,并有半数孕鼠中毒死亡。单给高剂量亚硝酸钠或乙基脲则不引起胚胎或孕鼠死亡。表明亚硝酸钠和乙基脲在大鼠体内合成N-亚硝基乙基脲,并通过胎盘引起胚胎死亡。前体物与胚胎毒性之间有明显的剂量反应关系。同时给孕鼠浓缩猕猴桃汁的各组在亚硝酸钠0.125-0.50mmol/kgBW者胚胎存活率无明显减少,仅最高剂量组活胎率明显减少,吸收胎率达58.6％,但无孕鼠中毒死亡。实验结果表明浓缩猕猴桃汁能明显阻断大鼠体内N-亚硝基乙基脲合成,预防所引起的胚胎毒性。     

常见蔬菜阻断N-亚硝基化合物(NC)形成的研究

在模拟胃内条件下,测定了茄子、黄瓜、球叶甘蓝、扁豆、番茄、灯笼椒、菠菜、胡萝卜、芹菜、葱头和大白菜11种常见蔬菜对N-二甲基亚硝胺形成的阻断作用。结果表明,在以氨基比林为前体,亚硝酸钠为亚硝化剂,pH3.00,37℃,反应一小时的反应体系中,多数蔬菜中天然存在的抗坏血酸可有效地阻断N-二甲基亚硝胺的形成。阻断率范围为32.07％～97.61％。其中以球叶甘蓝阻断率最低,灯笼椒阻断率最高,这和其所含抗坏血酸量的多少有关。葱头、扁豆、菠菜和茄子中除所含抗坏血酸外还有其他物质可阻断N-二甲基亚硝胺的形成,阻断率分别为77.91％、73.40％、57.48％和30.75％(已扣除蔬菜所含抗坏血酸的阻断作用);其阻断作用呈明显的剂量效应关系,相关系数分别为0.756、0.917、0.607和0.801。芹菜中含有促进N-二甲基亚硝胺形成的物质,其平均促进率为+34.00％。     

刺梨汁对脂质过氧化作用影响的研究

本文用体外和体内实验观察刺梨汁对脂质过氧化作用的影响。结果表明、体外实验中IC_(50)对CHP和CCl_4分别为45μl/ml及85μl/ml,而相当于刺梨汁中浓度的维生素C反而具有促进作用;刺梨汁对大鼠体内脂质过氧化本底水平及CCl_2致脂质过氧化作用无明显影响。刺梨汁体外抗脂质过氧化作用的有效成分有待进一步鉴定。     

食品和动物饲料中亚硝胺合成机理

食品和动物饲料或体内亚硝胺的合成反应可能有下述三种:(1)二级胺和亚硝酸的缩合作用;(2)三级的N-烷基化合物由于亚硝酸作用去掉两个烷氨基,随后亚硝基化;(3)由微生物酶催化的亚硝基化作用,使硝酸盐成为亚硝基化剂。作者对以上三种途径用实验证明如下: 1.氨基酸抑制二乙胺和亚硝酸盐生成二乙基亚硝胺: 作用物:所有溶液都以pH 4.2的醋酸盐缓冲液配制:二乙基氯化铵最后浓度为0.1 M;亚硝酸钠最后浓度亦为0.1 M;谷氨酸一钠最后浓度为0.12 M;胃蛋白酶水解的卵白蛋白为1.7%。混合溶液在37℃保温。每小时取样一次直到24小时。结果证明,当无氨基酸时,过量亚硝酸盐存在,则二乙基亚硝胺形成的量与二乙胺浓度成正比(胺浓度增加10倍可使亚硝胺形成增加10     

A comparative analysis of mutagenic activities of air samples collected from Riyadh before,during and after the Gulf War

Samples of air particulates were collected from the city of Riyadh in 1988 before the Gulf War, a few months after the torching of oil wells in Kuwait during 1991 and several months (in 1992) after the burning oil wells were fully capped. The air samples were collected on fibre glass filters (GF-A, pore size 1.6 mum) by using a RADECO air sampler. Filters were shredded, soaked and sonicated in acetone to dissolve the organic contents. The solid residues obtained after evaporation of acetone were redissolved in 5 ml volumes of fresh acetone and tested for mutagenic activity in the Ames Salmonella assay using the tester strain TA98 for histidine reversion (Ames 1979, Maron and Ames 1983). The mutagenicity assay was performed with and without metabolic activation provided by the S-9 fraction of an Aroclor-induced rat liver homogenate and co-factors. The results of this study showed that the pre-war samples of air particulates from Riyadh induced 11 histidine revertants/10 m3 of air analyzed, while the 1991 samples (during war) induced 40-50 revertants/10 m3 of air (4-5 times higher). However, the number of histidine revertants induced by the post-war (1992) samples came down to 10-11/10 m3 of air. These data, thus, strongly suggested that there was an increase in air particulate mutagenicity due to the atmospheric pollution of Gulf areas caused by the burning oil wells in Kuwait. This notion is supported by the fact that the mutagenic activity of air samples collected months after the burning oil wells were capped assumed the pre-war level. In view of the strong correlation between mutagenicity and carcinogenicity (McCann and Ames 1976) it would be expected that air pollution with mutagenic agents enhanced by the Gulf War would increase the carcinogenic risk for upper aerodigestive tracts in the exposed population in Kuwait and the surrounding areas. Such adverse health effects of mutagenic air pollutants generated by the burning oil wells in Kuwait should be assessed by proper epidemiologic studies.     

异丙草胺原药致突变性试验研究

目的探讨异丙草胺原药的致突变性,预测其遗传危害和潜在致癌作用的可能性。方法用昆明种小鼠经口灌胃染毒,骨髓微核试验的剂量分别为5000、2500、1250、625mg/kg,睾丸细胞染色体畸变试验的剂量为625.00、312.50、156.25mg/kg,分别取胸骨、睾丸组织,常规制片,镜下观察。鼠伤寒沙门氏菌回复突变(Ames)试验采用平板掺入法,剂量分别为0.5、1.0、2.0、5.0mg/皿。结果小鼠骨髓微核、睾丸细胞染色体畸变试验显示:异丙草胺原药染毒组与阴性对照组比较,差异无显著性(P>0.05);Ames试验显示各菌株的各剂量组的回变菌落数均未超过自发回变菌落数的两倍。结论在本试验条件下,未发现异丙草胺原药的致突变性。     

国产汽车尾气提取物的致突变性研究

采用ＴＡ９８和ＴＡ１００两种菌株检测汽车尾气中颗粒及气体冷凝提取物的致突变性，所有样品均有明显的致突变效应，以诱导ＴＡ９８菌株回变为主。综合比较，由于柴油车颗粒排放量高，每Ｌ排放物诱导的菌落回变数最高，除柴油车和吉普车外，其余汽油车尾气的间接诱变作用均以气体部分为主。     

松茸提取物体外抑制染发剂致突变作用

目的　寻找安全有效的抗突变生物资源 ,为降低染发剂致突变危害提供实验依据。方法　采用修改的Ames试验 ,观察真菌植物松茸提取物对染发剂致突变作用的影响。结果　松茸提取物能显著抑制染发剂的致突变作用 (P <0 0 1) ,对测试菌株TA97、TA98和TA10 0 的诱发回变菌落形成的抑制率最高分别达到 96 9% ,99 6 %和 95 4 % ,其抑制作用间存在明显的剂量 反应关系。结论　松茸提取物对染发剂致突变具有显著的抑制和抗突变作用     

Monitoring nitrite, N-nitrosodiethanolamine, and mutagenicity in cutting fluids used in the metal industry.

We carried out an integrated environmental/biological monitoring program to evaluate cancer hazards among metal industry workers exposed to cutting fluids. Several cutting fluids were sampled according to response to a semiquantitative nitrite rapid test in metal factories in central Italy. The nitrite-positive samples were analyzed for nitrite and nitrosodiethanolamine (NDELA) content and mutagenic activity. The nitrite-negative samples were analyzed only for mutagenicity. Of the total samples, 20.6% were nitrite positive, and all contained NDELA. However, nitrite content was not quantitatively predictive of the NDELA content, which varied enormously among samples (0.3-1900 mg/kg). Nitrite-negative samples were always nonmutagenic. Mutagenicity was found in half the NDELA-containing samples but was not related to nitrite or NDELA content. Nitrite screening of cutting fluids in the field is an interesting method for identifying samples that potentially contain NDELA and other unknown mutagens and, when performed with short-term mutagenicity tests, nitrite screening seems to be a valid tool by which industrial managers and health officers could minimize the health hazards associated with occupational exposure to cutting fluids.     

新型农用杀菌剂氰菌胺致突变实验研究

目的探讨氰菌胺原药的致突变作用。方法小鼠骨髓嗜多染红细胞微核试验分别以1000、500、250mg/kg剂量经口给药2d,小鼠睾丸初级精母细胞染色体畸变试验分别以2000、1000、500mg/kg剂量经口给药5d,观察骨髓嗜多染红细胞微核率及睾丸初级精母细胞染色体畸变率。鼠伤寒沙门杆菌回复突变试验(Ames试验),选用TA97、TA98、TA100和TA102菌株,试验剂量为5000、1000、200、40μg/皿,观察各菌株的回变菌落数。结果小鼠骨髓嗜多染红细胞微核率及小鼠睾丸初级精母细胞染色体畸变率与阴性对照组比较,差异均无统计学意义(P0.05)。Ames试验,氰菌胺原药各剂量组的回变菌落数均未超过自发回变菌落数的2倍,亦未见剂量-反应关系,Ames试验结果为阴性。结论上述致突变试验结果表明氰菌胺原药无致突变作用。     

Toxicological and chemical characterization of the process stream materials and gas combustion products of an experimental low-btu coal gasifier

The process gas stream of an experimental pressurized McDowell-Wellman stirred-bed low-Btu coal gasifier, and combustion products of the clean gas were characterized as to their mutagenic properties and chemical composition. Samples of aerosol droplets condensed from the gas were obtained at selected positions along the process stream using a condenser train. Mutagenicity was assessed using the Ames Salmonella mammalian microsome mutagenicity assay (TA98, with and without rat liver S9). All materials required metabolic activation to be mutagenic. Droplets condensed from gas had a specific mutagenicity of 6.7 revertants/microgram (50,000 revertants/liter of raw gas). Methylnaphthalene, phenanthrene, chrysene, and nitrogen-containing compounds were positively identified in a highly mutagenic fraction of raw gas condensate. While gas cleanup by the humidifier-tar trap system and Venturi scrubber led to only a small reduction in specific mutagenicity of the cooled process stream material (4.1 revertants/microgram), a significant overall reduction in mutagenicity was achieved (to 2200 revertants/liter) due to a substantial reduction in the concentration of material in the gas. By the end of gas cleanup, gas condensates had no detectable mutagenic activity. Condensates of combustion product gas, which contained several polycyclic aromatic compounds, had a specific mutagenicity of 1.1 revertants/microgram (4.0 revertants/liter). Results indicate that the process stream material is potentially toxic and that care should be taken to limit exposure of workers to the condensed tars during gasifier maintenance and repair and to the aerosolized tars emitted in fugitive emissions. Health risks to the general population resulting from exposure to gas combustion products are expected to be minimal.     

Handling of cytostatic drugs and urine mutagenesis

Summary As part of a French national epidemiologic study on human reproduction among hospital personnel, we investigated urine mutagenicity of nurses and personnel from oncology units exposed to cytostatic drugs. During a first series of experiments, urine mutagenicity of 47 subjects working in six oncology units was investigated in the Marseille regional's hospital. A control group of 37 individuals working in one cardiology clinic was also included. Urinary mutagens were extracted on XAD-2 resin and tested by two bacterial mutagenicity tests: the Ames test with tester strains Salmonella typhimurium TA 97, TA 98, TA 100 and TA 102 with or without metabolic activation (S9 MIX) and the SOS Chromotest with tester strain Escherichia coli PQ 37-S9 MIX. Bactericidal activity towards the tester strains was found in 40% of the urine samples (36/90). During a second series of experiments, urine mutagenicity of 17 office clerks was also investigated. Toxicity was found in six of the 21 urine samples. No significant difference of toxicity distribution and no relationship between toxicity and cigarette smoking were found. Qualitative analysis of the data showed no significant difference among the exposed groups and the control group (Chi 2 = 0.529, df = 2) with tester strain TA 98 + S9 MIX. Cigarette smoking was found to be the main factor of increased urinary mutagenicity (Chi 2 = 0.529, df = 1). Quantitative analysis of the data showed that mutagenic potencies varied from 0.332 ±0.539 revertants/mg creatinine to 7.226 ± 6.743 revertants/mg creatinine with TA 98 + S9 MIX. A relationship between the number of cigarettes smoked and mutagenic potency was found (Spearman rank coefficient r _s = 0.412, P < 0.05). One urine sample was found to be mutagenic with tester strain TA 102 and PQ 37.