Lack of effect of selenium on induction of tumors of esophagus and bladder in rats by two nitrosamines

The effect of differences in level of dietary selenium on the induction of esophageal and bladder tumors in rats by two nitrosamines was investigated. Groups of 20 female F344 rats were given a synthetic diet containing less than 0.05 ppm Se to which selenium (as sodium selenite) was added at the concentration of 0.35, 0.7, 1.4 and 2.1 ppm selenium. These four groups, plus one without added Se, were treated with 20 ml per rat per day, 5 days a week, of a solution of nitrosomethylcyclohexylamine containing 5 mg/liter. A parallel five groups were treated in the same way with a solution of nitrosomethyl-3-carboxypropylamine in drinking water containing 600 mg per liter, as drinking water. Treatment lasted 28 weeks, at which time some animals had developed tumors. A group of 20 rats fed 0, 1.4 and 2.1 ppm Se was not treated with carcinogen. Rats consuming 1.4 ppm or 2.1 ppm Se gained weight more slowly than other groups. There was no significant difference in survival between the five groups treated with each carcinogen but receiving different dietary levels of selenium. Neither was there any significant difference between groups receiving each carcinogen in the incidence of tumors of the esophagus induced by nitrosomethylcyclohexylamine or of tumors of the urinary bladder induced by nitrosomethylcarboxypropylamine. Control rats on the synthetic diets did not survive as well as untreated rats eating regular chow diet. In these conditions there was no effect of dietary selenium levels on the induction of tumors in female rats by the two carcinogenic nitrosamines we used.     

Effects of cyanide on selenium metabolism in rats

Adult male rats were given drinking water containing either 0 or 150 ppm cyanide for 2 weeks. They were then injected with 5 microCi 75Se-selenite, and excretion of radioactivity in urine and feces was determined. No difference in excretion of 75Se occurred during the rapid phase, but the cyanide-treated rats (T1/2 28 days) excreted significantly more 75Se in urine than control (T1/2 38 days) rats. Cyanide had no effect on excretion of 75Se in feces or on the distribution of 75Se in cytosolic proteins in liver, kidney, muscle or testes. In a second experiment weanling male rats were given water with either 0 or 150 ppm cyanide and were killed for glutathione peroxidase assay and selenium analysis in blood, kidney, liver, muscle and testes after 3, 6 or 9 weeks of treatment. Glutathione peroxidase activity and selenium concentrations were significantly reduced by cyanide in all tissues except testes.     

Carcinogenicity and chronic toxicity in mice and rats administered vinyl acetate monomer in drinking water

Carcinogenicity and chronic toxicity of vinyl acetate monomer (VA) were examined in male and female Crj:BDF1 mice and F344/DuCrj Rats. Groups of 50 mice and 50 rats of each sex were orally administered VA in drinking water containing 0, 400, 2,000 or 10,000 ppm (g/g) VA for 104 wk. Squamous cell tumors were clearly evident in the upper digestive tract of treated mice and rats, and in the larynx of treated mice of both sexes. In mice, squamous cell carcinomas and papillomas were observed in the oral cavity, esophagus, forestomach and larynx of the 10,000 ppm group, together with basal cell hyperplasia, squamous cell hyperplasia and epithelial dysplasia. In rats, incidences of squamous cell carcinomas and papillomas were increased in the oral cavity of the 10,000 ppm group of both sexes, and an esophagus squamous cell carcinoma was observed in a 10,000 ppm female. Pre-neoplastic hyperplasias were also noted. Mapping of the neoplastic and pre-neoplastic lesions in the oral cavity of the 10,000 ppm group revealed that both the lesions occurred predominantly at Level V in mice and at Level VI in rats. A lower confidence limit of a benchmark dose (BMDL10) of 477 mg/kg/d was obtained from a dose-response relationship between combined incidence of squamous cell carcinomas and papillomas in the oral cavity of mice and rats and the estimated daily VA intakes per body weight, and compared with literature values.     

不同膳食硒水平对甲基苄基亚硝胺(NMBzA)诱发大鼠食道肿瘤及小鼠前胃肿瘤的影响

本实验对膳食中不同硒含量与NMBzA诱发大鼠食道肿瘤及小鼠前胃肿瘤的关系进行了研究。分别将断乳Wistar大鼠和断乳昆明种小鼠随机分成缺硒(硒含量<0.02ppm)组;正常硒(0.2ppm)组;补硒(2.0ppm)组;和对照组(0.2ppm)。除对照组外,各组动物灌胃给予NMBzA。其中大鼠自第5周至第18周实验结束,每周一次给药3mg/kg体重,小鼠第2～7周,每周一次给药1mg/kg体重,第8～12周,每周二次,每次0.7mg/kg体重。实验结束时分别进行病理学检查。结果大鼠食道肿瘤及小鼠前胃肿瘤发生率在各实验组间无显著性差异。     

慢性氟中毒大鼠体氟积累排泄动态变化及硒的影响

Ｗｉｓｔａｒ大鼠饮３０和５０ｍｇ／Ｌ高氟（Ｆ）水造成慢性氟中毒，同时另外两组大鼠饮高Ｆ水、饲２ｍｇ／ｋｇ加硒（Ｓｅ）饲料。１年内每月测饮水、摄食和排尿量，而后计算其日平均摄Ｆ、排Ｆ量，并每月测尿液Ｆ含量。喂养至４、８、１４个月时将大鼠分３批处死，测尿液、肝脏、血清Ｓｅ和骨骼、肝脏、肾脏、血清Ｆ含量。结果两组氟中毒大鼠与对照组比较摄Ｆ量升高，排Ｆ／摄Ｆ比值降低。尿Ｆ的升高与水Ｆ浓度及饮Ｆ时间呈正相关。骨、肝Ｆ大量蓄积出现于氟中毒中期，血Ｆ在氟中毒晚期明显上升。同未加Ｓｅ氟中毒大鼠比较，两组加Ｓｅ组大鼠尿、肝、血Ｓｅ升高。与此同时大鼠摄食、饮水状况改善，体重增加；排尿量升高；尿Ｆ排泄量和排Ｆ／摄Ｆ比显著提高；同时骨、肝、肾和血清Ｆ含量降低。     

硒镉摄入对大鼠脏器中硒、镉、铜、锌、锰含量的影响

目的：探讨硒镉摄入对大鼠脏器中硒、镉、铜、锌、锰含量的影响。方法：用含5ppm硒、50ppm镉和含5ppm硒＋50ppm镉的水,供3月龄的Wistar雄性大鼠自由饮用,3周后用原子吸收分光光度法测定大鼠肝、肾、脾和睾丸中硒、镉、铜、锌和锰的含量。结果：5ppm硒组大鼠4种组织中硒、铅含量、肝脾组织中锌含量和肾、脾、睾丸组织中铜含量均高于对照组;50ppm镉组大鼠4种组织中镉的含量、肾脾组织中硒的含量和肝脾组织中铜锌含量均高于对照组;经口同时摄入硒、镉时大鼠4种脏器组织中硒的含量明显低于硒组,4种脏器组织中镉的含量明显高于硒组,肝脏组织中锌的含量显著低于镉组,脾脏组织中锌的含量显著低于硒组,肾、脾、睾丸组织中铜的含量低于硒组,肾、睾丸组织中锰的含量低于镉组。     

Inhibition by selenium of intrahepatic cholangiocarcinoma induction in Syrian golden hamsters by N'-nitrosobis(2-oxopropyl)amine.

The effects of selenium supplementation on induction of cholangiocarcinomas and related precancerous lesions in female Syrian Golden hamsters by N'-nitrosobis(2-oxopropyl)amine (BOP) were investigated. Four-week-old animals were divided into two groups according to the selenium level contained in the drinking water (0.1 ppm or 4.0 ppm) and fed a purified diet containing less than 0.05 ppm of the trace element. Starting at Week 4 of the experiment, hamsters were administered 10 weekly injections of BOP (10 mg/kg body wt) and then killed 18 weeks after the last carcinogen administration. Animals receiving physiological saline alone served as controls. Cholangiocellular carcinomas tended to be reduced, and putative preneoplastic lesions of cholangiofibrosis were significantly decreased in the high-as opposed to the low-selenium groups in terms of both incidence rate and number per effective animal. The respective high and low selenium values for incidence and number were 24/38% and 0.34/0.66, respectively, for cholangiocarcinomas and 50/89% and 1.21/8.44, respectively, for cholangiofibroses. Proliferation of intrahepatic bile ducts was also significantly inhibited in the high-selenium group along with cyst formation. Biochemical investigation revealed both selenium level and glutathione peroxidase activity to be significantly greater in the high-than in the low-selenium group livers. The results thus suggest that selenium may inhibit BOP-induction of bile duct lesions, possibly via glutathione peroxidase-mediated alteration of carcinogenesis.     

Lack of effects of selenium on N-nitrosomethylbenzylamine-induced tumorigenesis, DNA methylation, and oncogene expression in rats and mice.

The effects of dietary selenium deficiency and excess on N-nitrosomethylbenzylamine-(NMBA) induced esophageal neoplasia in rats and forestomach tumors in mice and the effects of dietary selenium on DNA adduct formation and on the activities of DNA adduct-repairing enzyme and oncogene expression in rat esophagus were investigated. The esophageal and forestomach tumors were induced by administration of NMBA by gavage with a total dose of 39 mg/kg body wt in rats and 12 mg/kg body wt in mice. Neither selenium dietary deficiency (Se < 0.02 ppm) nor selenium excess (2.0 ppm) showed any significant effect on the incidence of tumors or number of tumors per tumor-bearing animal. For the DNA adduct formation studies, rats were given a dose of NMBA intraperitoneally after six weeks on the different selenium-containing diets. No significant difference in the amount of the DNA adduct O6-methyldeoxyguanosine was found among the different selenium-treated groups. In a parallel group of rats that did not receive NMBA, the levels of esophageal O6-methyldeoxyguanosine DNA methyltransferase were not significantly altered by dietary selenium levels. The c-myc oncogene expression in rat esophagus was induced by the administration of NMBA (3 mg/kg body wt) by gavage once a week for eight weeks. Dietary selenium did not show any effects on its expression. On the basis of the results of these studies, dietary selenium has no effects in the NMBA-induced tumor model.     

Effect of chronic selenite supplementation on selenium excretion and organ accumulation in rats

We examined the effect of chronic selenite supplementation on whole body and selected organ selenium (Se) accumulation, urine excretion of total Se and trimethylselenonium ion, and Se balance in adult male rats. Animals were housed in metabolic cages and given either deionized water or water containing 4 micrograms of Se/mL as selenite for 30 d. Absorption of selenite was nearly complete, with only approximately 10% of ingested Se appearing in feces. There was a rapid rise in urinary Se that reached a plateau within a few days and accounted for 54 +/- 2% of the intake. Excretion of trimethylselenonium ion (TMSe) in urine increased rapidly, representing 35-40% of urinary Se in the supplemented animals compared with only 2% for the control group. In one experiment, rats were killed at 30 d and total carcass Se was measured using isotope dilution analysis. Supplemented rats had only a modest increase in whole body Se (94 +/- 4 micrograms Se vs. 66 +/- 3 in controls). Calculation of Se balance in the supplemented rats showed that approximately 35% of ingested Se could not be accounted for by urine plus fecal losses combined with the portion retained in the carcass. The results from this study demonstrate that under the condition of supplementation at 4 micrograms of Se/mL of drinking water, pathways other than urinary and fecal excretion may account for a substantial portion of Se loss.     

Effect of dietary selenium on plasma selenoprotein P, selenoprotein P1 and glutathione peroxidase in the rat

The purpose of this study was to determine the effect of dietary selenium on the abundance of selenium in plasma selenoprotein P, selenoprotein P1 and glutathione peroxidase. Weanling rats were provided water that contained 1.0, 0.1 or 0.01 ppm selenium and 75Se for 21 days. Gel filtration of denatured subunits was used to identify 75Se in the selenoproteins. Rats provided 1.0 ppm selenium accumulated 1.5 times more 75Se in liver cytosolic selenoprotein P1, but not in the two other selenoproteins, than did rats provided 0.1 ppm selenium. Most of the liver and blood selenium in rats provided 1.0 ppm selenium was insoluble and in an unknown chemical form. The tissue accumulation of unrecoverable selenium was apparently a response to the high dietary level of selenium. The proportion of selenium in plasma selenoprotein P, a putative selenium-transport protein, reflected the long-term selenium status of rats and varied from approximately 11-58% depending on the level of selenium supplementation. Turnover of selenium from this protein was affected by the dietary selenium of the rats. The results indicate that selenium incorporation into plasma selenoprotein P and selenoprotein P1 is affected by diet in ways that may reflect their importance to the rat.     

The effect of Cu, Zn, Mn, on selenium content in the liver, brain, blood and kidney of mice]

The influence of dietary copper, zinc and manganese on the contents of selenium in liver, brain, and kidney of 150 mice was studied. The mice were divided into 5 groups with different trace elements in their forage (I. 40ppm Cu+4ppm Se, II. 100ppm Zn+4PPm Se, III. 4ppm Mn+4ppm Se, IV. control group). Every 10 mice were killed at one month intervals in each group and the contents of selenium in liver, brain, kidney and blood were determined. The selenium contents of blood, kidney in I, II groups were significantly lower than in IV group. The selenium content of liver was also significantly lower than IV group in two months, but no difference in the third month. No change of selenium content in brain had been observed.     

Interactive effects of arsenate,selenium, and dietary protein on survival,growth, and physiology in mallard ducklings

High concentrations of arsenic (As) and selenium (Se) have been found in aquatic food chains associated with irrigation drainwater. Total biomass of invertebrates, a major source of protein for wild ducklings, may vary in environments that are contaminated with selenium. Day-old mallard (Anas platyrhynchos) ducklings received an untreated diet (controls) containing 22% protein or diets containing 15 ppm Se (as selenomethionine), 60 ppm Se, 200 ppm As (as sodium arsenate), 15 ppm Se with 200 ppm As, or 60 ppm Se with 200 ppm As. In a concurrent experiment, the same sequence was repeated with a protein-restricted (7%) but isocaloric diet. After 4 weeks, blood and tissue samples were collected for biochemical and histological examination. With 22% protein and 60 ppm Se in the diet, duckling survival and growth was reduced and livers had histopathological lesions. Arsenic alone caused some reduction in growth. Antagonistic interactive effects occurred between As and Se, including complete to partial alleviation of the following Se effects: mortality, impaired growth, hepatic lesions and lipid peroxidation, and altered glutathione and thiol status. With 7% protein, survival and growth of controls was less than that with 22% protein, Se (60 ppm) caused 100% mortality, and As (200 ppm) caused mortality, decreased growth, and liver histopathology. These findings suggest the potential for antagonistic effects of Se and As on duckling survival, growth, and physiology with adequate dietary protein but more severe toxicological effects when dietary protein is diminished.     

Effects of selenium supplementation on hepatocarcinogenesis in rats

Four groups of weanling male Wistar rats (Groups A-D) received diethylnitrosamine (DEN, 40 ppm) in their drinking water for four weeks; after a recovery period of two weeks, they received (for the rest of the experiment) phenobarbital (PB, 500 ppm) added to a Torula yeast-based diet containing 0.17 ppm of selenium. Dietary selenium (2 ppm), as sodium selenite, was given to Group B one week before and during DEN treatment, to Group C one week before and during PB treatment, and to Group D during the entire experiment. Groups A and E received the unsupplemented diet, whereas Group E was not treated with DEN or PB. Pair-feeding conditions were used to minimize possible influences of differences in food intake and growth. Rats were killed at the 19th and 24th weeks after the experiment began. No significant differences were found in food and fluid intakes or in growth rates among the groups. Livers in Group E were histologically normal, whereas preneoplastic and neoplastic lesions were found in all other groups. In rats killed at the 19th and 24th weeks, the numerical and the volumetric densities of preneoplastic lesions did not differ significantly between all the groups. Similarly, the incidence of hepatocellular carcinomas only detected at 24 weeks was not significantly different between the groups. These results indicated that in this particular model of hepatocarcinogenesis, the dietary supplementation of 2 ppm of selenium did not modify the development of preneoplasia and carcinomas.     

Antioxidant enzyme response to selenium deficiency in rat myocardium.

Influences of dietary selenium (Se) deficiency, physical training and an acute bout of exercise on myocardial antioxidant enzyme activity, lipid peroxidation and related biochemical properties were investigated in post-weanling male Sprague-Dawley rats. An experimental group was fed a diet containing less than 0.01 mg Se/kg and had free access to distilled water (Se-D), whereas control rats were supplemented with 0.5 mg Se/l in drinking water (Se-A). Se deficiency depleted heart mitochondrial and cytosolic Se-dependent glutathione peroxidase activity to 24 and 3%, respectively, of those in Se-A rats. Heart mitochondrial superoxide dismutase (Mn SOD) activity was 24% higher (p less than 0.05) in Se-D than in Se-A rats. Cytosolic (copper-zinc) SOD and catalase activities were not altered, whereas glutathione S-transferase activity was significantly decreased in Se-D (p less than 0.01). Myocardial antioxidant enzyme activities were not affected by either training or an acute exercise bout. Heart lipid peroxidation and activities of several enzymes in substrate metabolism were also unaffected by Se or exercise. It is concluded that rat heart has sufficient reserve of antioxidant enzyme capacity in coping with oxidative stress imposed by Se deficiency or exercise. The adaptation of Mn SOD may reveal its potential role in myocardial antioxidant defense.     

Fluoride-selenium interaction in the hard and soft tissues of the rat.

The interaction of dietary fluoride and selenium in the hard and soft tissues of rats was studied by providing drinking solutions containing 50 ppm F, as NaF, alone or plus 1 or 3 ppm Se as one of the following selenium compounds: NaSeO3, Na2SeO4, DL-selenomethionine, or DL-selenocystine. The following parameters were measured: symptoms of selenium toxicity, soft tissue uptake of fluoride and selenium, histology of liver and kidney tissues, fluoride uptake into growing femur bones, and fluoride uptake onto calcified molar enamel. No evidence was found that fluoride interacted with any of the four selenium compounds.     

Effects of selenium supplementation on hepatocarcinogenesis in rats

Four groups of weanling male Wistar rats (Groups A—D) received diethylnitrosamine (DEN, 40 ppm) in their drinking water for four weeks; after a recovery period of two weeks, they received (for the rest of the experiment) phenobarbital (PB, 500 ppm) added to a Torula yeast‐based diet containing 0.17 ppm of selenium. Dietary selenium (2 ppm), as sodium selenite, was given to Group B one week before and during DEN treatment, to Group C one week before and during PB treatment, and to Group D during the entire experiment. Groups A and E received the unsupplemented diet, whereas Group E was not treated with DEN or PB. Pair‐feeding conditions were used to minimize possible influences of differences in food intake and growth. Rats were killed at the 19th and 24th weeks after the experiment began. No significant differences were found in food and fluid intakes or in growth rates among the groups. Livers in Group E were histologically normal, whereas preneoplastic and neoplastic lesions were found in all other groups. In rats killed at the 19th and 24th weeks, the numerical and the volumetric densities of preneoplastic lesions did not differ significantly between all the groups. Similarly, the incidence of hepatocellular carcinomas only detected at 24 weeks was not significantly different between the groups. These results indicated that in this particular model of hepatocarcinogenesis, the dietary supplementation of 2 ppm of selenium did not modify the development of preneoplasia and carcinomas.     

Effects of dietary selenium and vitamin E on hepatic mixed-function oxidase activities and in vivo covalent binding of aflatoxin B1 in rats

Male weanling fischer-344 rats were fed a selenium (Se)-vitamin E (VE) deficient Torula yeast basal diet or that diet supplemented with a graded levels of SE (0.2-6.0 ppm as Na2SeO3) or VE (100 iu/kg as all-rac-2-tocopheryl acetate), or both, for 4 or 6 weeks. Se deficiency and excess (6.0 ppm) markedly depressed in vivo covalent binding of aflatoxin (AFB1) to macromolecules in livers of rats killed 2 hours after an i.p. dose of 1 mg/kg tritiated AFB1. VE supplementation had no effect. Prior phenobarbital (PB) treatment generally decreased adducts without changing diet-related trends. Some hepatic enzyme capabilities were also measured. Cytochrome b5 content and cytochrome c reductase activity were unaffected by diet. VE increased cytochrome P-450 content, ethylmorphine N-demethylase and benz(alpha)pyrene hydroxylase activities; all these were unaffected by Se levels. Se deficiency and excess (but not VE deficiency) increased glucuronyl transferase. PB induction affected all diet groups and was more in agreement with MFO activity than transferase. Adduct formation was more consistently related to transferase activity than to MFO activities. The contrasting effects of SE and VE on AFB1 adducts in rats and chicks are discussed.     

Toxic Effects of Trace Elements on the Reproduction of Mice and Rats

Breeding mice and rats were exposed to low doses of six trace elements in drinking water in an environment controlled as to contaminating trace metals. Each group was carried through three generations. Compared to control mice given only doubly deionized wafer, selenafe (3 ppm selenium) resulted in excess deaths before weaning, runts, and failures to breed. Lead (25 ppm) and cadmium (10 ppm) resulted in loss of the strain in two generations with many abnormalities. Molybdate (10 ppm molybdenum) was slightly toxic in this respect, and arsenic resulted only in elevated ratios of males to females. In rats, lead was very toxic, and titanium and nickel moderately toxic, resulting in many early deaths and runts. This method provides fairly rapid estimates of innate toxicities of trace elements in doses tolerable for growth and survival.     

李沧区健康成人血中7种金属元素参考值调查

目的:描述青岛市李沧区健康成人全血中Zn、Fe、Cu、Mn、Mo、Se、Ca的含量及其分布特点,确定其在全血中的正常参考值范围。方法:采用微波消解—电感耦合等离子体质谱仪进行测定,数据使用SPSS11.5统计处理。结论:李沧区健康成人全血中金属元素的总体范围:Ca为41.4~64.7 mg/L、Fe为369.1~567.4mg/L、Zn为3.23~6.62 mg/L、Cu为0.602~1.068 mg/L、Mn为5.5~46.3μg/L、Mo为0.22~3.54μg/L、Se为62.2~143.1μg/L;其中,Fe、Zn、Cu呈正态分布,而Ca、Se、Mn、Mo呈偏态分布;正常参考值范围:男性Ca(mg/L):46.9~61.1,女性Ca(mg/L):43.1~64.5;男性Se(μg/L):63.3~134.5,女性Se(μg/L):65.6~135.8;男性Zn(mg/L):4.33~6.41,女性Zn(mg/L):3.52~5.52;男性Fe(mg/L):386.1~546.5,女性Fe(mg/L):386.6~492.5;男性Cu(mg/L):0.614~0.970,女性Cu(mg/L):0.694~1.030;Mn(μg/L):6.08~28.34;Mo(μg/L):0.22~1.54。