Effect of selenium on virally induced and transplantable tumor models

Se is effective in inhibiting both virally induced and transplantable tumors. Continued intake of Se at quantities greater than those required to optimize growth and glutathione peroxidase (EC 1.11.1.9) activities appear to be needed to achieve maximal tumor inhibition. Differences in the sensitivity to Se of various tumor cell lines are evident. The efficacy of Se depends on the form and mode of administration of this trace element. Total tumor mass also appears to affect the efficacy of Se. Evidence now suggests that selenodiglutathione or some other intermediate in Se metabolism is responsible for the antitumorigenic properties of this trace element.     

Effects of dietary selenium and of lead on the genesis of spontaneous mammary tumors in mice

Selenium added to the diet significantly lowers the incidence of spontaneous mammary adenocarcinoma in female inbred C3H/St mice infected with the Bittner Milk Factor. Lead, 5 ppm, added to the drinking water in the form of the acetate, diminishes the uptake of selenium and reduces its anticarcinogenic effects, causing mammary tumors to appear with the same high incidence as in Se-unsupplemented controls. At higher lead concentrations in the drinking water (25 ppm), the overall tumor incidence is lowered, but tumor growth is significantly accelerated and the survival of tumor-bearing mice is shortened. Under the conditions of administration chosen, lead acts as a selenium antagonist and lowers the concentrations of selenium in liver, kidney, and spleen. The deposition of selenium, copper, and arsenic in bone is increased as compared to lead-unexposed controls.     

Effect of selenium supplementation on platelet selenium,glutathione peroxidase,and aggregation

The selenium content of platelets is extremely high. About half of this selenium originates from irreversible incorporation by bone marrow precursor cells, which satisfy their need for selenium even under conditions of marked selenium deficiency. In order to study the effect of increased dietary selenium supply on the concentration of selenium, glutathione peroxidase (GSH-Px-) activity, and aggregability of platelets, normal healthy subjects were supplemented with 300 μg of selenium as Se-rich yeast/d for 3 mo. No significant effect of Se supplementation on platelet Se and GSH-Px were observed, whereas erythrocytes accumulated Se without reaching saturation. Although platelet aggregability was variable during the period of observation, this was traced back to factors other than selenium, including environmental temperature. This study demonstrates that the selenium concentration of platelets is subject to tight physiological control also at high dietary selenium intakes.     

Effects of amphetamine on the development of MTV-induced mammary tumors in female mice.

Female C3H/He mice carrying the mammary tumor virus (MTV) were monitored for mammary tumor incidence and latent periods while submitted to a daily subcutaneous injection with amphetamine (0,4 mg/kg/day). Results show that amphetamine caused an increase in incidence and a decrease in latency of tumors compared with placebo. There was also appreciated a correlation with the lethality of mice.     

Effect of selenium compounds and thiols on human mammary tumor cells

The effect on cell viability and growth rate of sodium selenite, selenocystine, sodium selenate, and selenomethionine at selenium concentrations of 6.25 and 12.5 uM was studied in vitro on cells of the human mammary tumor cell line HTB123/DU4475. Selenite and selenocystine affected both cell viability and growth rate of the tumor cells at these selenium concentrations. Selenite and selenocystine decreased intracellular glutathione concentrations, but did not affect tumor cell glutathione peroxidase activity. After six days of exposure to either selenate or selenomethionine, the viability of tumor cells remained stable, but cell growth, as measured by numbers of cells, was retarded. Neither selenate nor selenomethionine produced changes in concentrations of intracellular glutathione. The toxic effect of selenite on tumor cells was enhanced by addition of 0.25 mM glutathione to the growth medium. Preincubation of the tumor cells with 62.5 uM buthionine sulfoximine decreased cellular glutathione to 15% of controls at 24 h and enhanced the toxicity of selenite toward the tumor cells. Glutathione, 2-mercaptoethanol, and L-cysteine were all toxic to the tumor cells in a dose-dependent manner.     

Interactive effects of selenium and chromium on mammary tumor development and growth in MMTV-infected female mice and their relevance to human cancer

Evidence for interactive effects of chromium and selenium on the appearance of mammary tumors was obtained by exposing female virgin C₃H mice infected with the murine mammary tumorvirus (MMTV) to subtoxic levels of Cr [as Cr(III) nitrate] and Se (as sodium selenite) in the supply water. Cr counteracted the inhibitory effect of Se on tumor development in a dose-dependent manner, shortened the tumor latency period, and accelerated tumor growth rates. Exposure to Cr also altered the levels of Se in the liver and kidneys of the mice, indicating that Cr interacts with Se and affects its organ distribution. Chromium must be added to the list of Se-antagonistic elements that weaken or abolish the antitumorigenic effects of Se. These findings are relevant to human cancer as previous studies revealed the age-corrected mortalities from breast and other major forms of cancer in different countries to be inversely correlated with the dietary Se intakes, and directly correlated with the estimated intakes of Cr and of other Se-antagonistic elements. The presence of these elements in foods must be taken into account when estimating the optimal dose of supplemental Se for cancer risk reduction.     

Selenium and cancer: effects of selenium and of the diet on the genesis of spontaneous mammary tumors in virgin inbred female C3H/St mice

Inbred female C3H/St mice exhibit the normal incidence of spontaneous mammary adenocarcinoma of 80--100% if they are maintained on a standard commercial laboratory diet containing 0.15 ppm of selenium with meat and dried skimmed milk as major sources of protein. The tumor incidence drops to 42% if animals of the same strain are kept on a diet containing 0.45 ppm of selenium, with fishmeal as the main source of protein. The tumor incidence declines further to 25, 19 and 10% if the animals in addition receive 0.1, 0.5, and 1.0 ppm of selenium in the drinking water. Selenium supplementation at these levels has no noticable adverse effects on weight-grains and survival of the mice. Selenium supplmented groups of animals also remained tumor-free for longer periods than the unsupplemented controls. The results of this study indicate that a diet rich in seafoods and cereals provides more selenium and may in turn lower the probability of cancer development. Reference is made to the average human diet in the U.S.A., which only contains 0.07--0.15 ppm of selenium due to the comparatively low consumption of cereals and seafoods. An equivalent mouse diet would not have any cancer-protecting effect in the C3H/St mice of our study. Australian workers have reported significantly lower tumor incidence in a different strain of C3H mice if it was kept in Australia rather than in the U.S.A. We have found that the Australian feed contained three times more selenium than that employed in the U.S.A. and propose that this difference in selenium content was primarily responsible for these previous observations.     

Effect of selenium supplementation on mice infected with LP-BM5 MuLV, a murine AIDS model

LP-BM5 Murine leukemia virus (MuLV) infection of C57BL/6 mice develop a disease that has many features in common with human acquired immunodeficiency syndrome (AIDS), in particular abnormal lymphoproliferation and severe immunodeficiency. Thus, this MAIDS model may be useful for evaluation of potent antirival agents in vivo. Deficiency in antioxidant micronutients such as selenium, zinc, and glutathione have been observed in AIDs and AIDS-related complex (ARC) patients. In the present study, the MAIDS model was used to evaluate immunological and oxidative effect of Se as sodium selenite. Results indicated that Se treatment 0.1 mg/kg/d (p.o.) inhibited splenomegaly and sera IgG elevation effectively. In addition to abnormal immunity, oxidative imbalance possibly existed in MAIDS model, as lipid peroxide increased significantly in spleen and whole blood glutathione peroxidase (GSH-Px) activity decreased markedly. Se supplementation had good protective effect.     

Effect of vitamin E and selenium supplementation of cockerel diets on glutathione peroxidase activity and lipid peroxidation susceptibility in sperm, testes, and liver

The phospholipids of avian spermatozoa are characterized by high proportions of arachidonic (20:4n-6) and docosatetraenoic (22:4n-6) fatty acids and are therefore sensitive to lipid peroxidation. α-Tocopherol and glutathione peroxidase [GSH-Px] are believed to be the primary components of the antioxidant system of the spermatozoa. The present study evaluates the effect of vitamin E and vitamin E plus Se supplementation of the cockerel diet on GSH-Px activity, vitamin E accumulation, and lipid peroxidation in the spermatozoa, testes, and liver. At the beginning of the experiment 75 Rhode Island Red cockerels were divided into five groups, kept in individual cages, and fed a wheat-barley-based ration balanced in all nutrients. Supplements fed to the different groups were as follows: vitamin E, 0, 20, 200, 20, and 200 mg/kg to groups 1–5, respectively, with groups 4 and 5 also receiving 0. 3 mg Se/kg. The vitamin E supplementation produced increased levels of α-tocopherol in semen, testes, and liver. The inclusion of the Se into the cock diet had a significant (P < 0.01) stimulating effect on GSH-Px activity in seminal plasma, spermatozoa, testes, and liver. The increased vitamin E concentration in the spermatozoa was associated with a reduction in their susceptibility to lipid peroxidation. Similarly, the increased GSH-Px activity provided enhanced protection against lipid peroxidation.     

Effect of serum on cells cultured from human mammary tumors

Summary Clusters of cells derived from biopsy specimens of human mammary ductal carcinomas form two morphologically distinct epithelial colonies in culture, designated as E and E′. The proportion of E′ cell clusters that attached and formed colonies ranged from 0.3 to 13.0% with different tumors. Attachment was independent of tumor grade. Microscopic observations revealed that the survival of E′ cell colonies was limited to approximately 10 days with rapid cell degeneration commencing about 7 days. A comparison of sera showed that colony formation by cells from malignant tumors during the 1st week of culture was maximum in the presence of fetal bovine serum. Human serum alone was 70 to 100% less effective in promoting E′ colonies. The most significant finding was that human serum from normal donors inhibited E′ colony development in the presence of FBS. Although human serum was less effective than FBS in promoting colony formation by clusters of E cells, an inhibition was not observed. Inhibitory activity could not be attributed to either antagonistic hormones or the source of human serum. THese results demonstrate that normal human serum contains a factor(s) that exhibits an inhibitory activity specific for human epithelial cells (E′) derived from malignant tumors. Supported by NCI Contract CB-33898 and a Fellowship from the Imperial Cancer Research Fund, London, England.     

Effect of corticosteroids on arachidonate induced mortality in male and female mice

Sodium arachidonate (50 mg/kg) given intravenously to male and female mice induces pulmonary emboli followed by respiratory distress and cyanosis. Female mice are significantly more resistant to this treatment than male mice. Cortisone pretreatment for four days to intact mice (10 mg/kg/day/4 days) had a significant protective effect in both males and females against arachidonate toxicity, eliminating the sex difference previously observed. Adrenalectomy four days before arachidonate infusion increased the sensitivity to SA and resulted in 100% mortality in both sexes. Pretreatment of adrenalized animals with cortisone significantly reduced to some degree the mortality rate in both sexes. Castration of male and female mice three weeks before adrenalectomy did not affect the mortality rate seen following adrenalectomy alone. In conclusion, exogenous cortical steroids augment the resistance of even intact mice and are absolutely necessary for survival in adrenalectomized animals. The observed sex differences in untreated intact animals is not seen after treatment with cortisone or adrenalectomy.     

Effects of low selenium diets on antioxidant status and MPTP toxicity in mice

To investigate the role of chronic oxidative stress in MPTP neurotoxicity, C57BL mice were maintained 6–8 weeks on diets deficient in nutrients essential to cellular antioxidant defenses, selenium (Se) and alpha-tocopherol (vit E), and the effects on tissue antioxidant status and MPTP toxicity were evaluated relative to controls on supplemented diets. Activities of the major antioxidant enzymes, glutathione peroxidase (GPx), catalase, and superoxide dismutase, and levels of malondialdehyde as a marker for oxidative stress, were measured in brain, lung, liver and blood. Caudate depletion of dopamine and its metabolites served as a measure of MPTP neurotoxicity. For mice on the Se deficient diet, levels of the selenoenzyme GPx decreased from 50% in brain to 90% in blood. No compensatory changes in the activities of the other antioxidant enzymes were observed and addition of vit E to the diet did not alter antioxidant enzyme activities or malondialdehyde levels. In animals not treated with MPTP, the Se deficient diet significantly increased malondialdehyde only in liver. No protective effect of the antioxidant supplements against caudate depletion of dopamine and its metabolites was observed. However, malondialdehyde levels were increased in the brains of MPTP treated mice on the low Se diets, suggesting the possibility of secondary oxidative damage to tissues accompanying the destruction of substantia nigra neurons by MPTP.     

Effect of serum on cells cultured from human mammary tumors.

Clusters of cells derived from biopsy specimens of human mammary ductal carcinomas form two morphologically distinct epithelial colonies in culture, designated as E and E'. The proportion of E' cell clusters that attached and formed colonies ranged from 0.3 to 13.0% with different tumors. Attachment was independent of tumor grade. Microscopic observations revealed that the survival of E' cell colonies was limited to approximately 10 days with rapid cell degeneration commencing about 7 days. A comparison of sera showed that colony formation by cells from malignant tumors during the 1st week of culture was maximum in the presence of fetal bovine serum. Human serum alone was 70 to 100% less effective in promoting E' colonies. The most significant finding was that human serum from normal donors inhibited E' colony development in the presence of FBS. Although human serum was less effective than FBS in promoting colony formation by clusters of E cells, an inhibition was not observed. Inhibitory activity could not be attributed to either antagonistic hormones or the source of human serum. These results demonstrate that normal human serum contains a factor(s) that exhibits an inhibitory activity specific for human epithelial cells (E') derived from malignant tumors.     

Effect of selenium supplementation on polyunsaturated fatty acids in rats

The purpose of this work was to study plasma, adipose tissue, and liver fatty acids percentages of Wistar rats that drank water supplemented with several levels of sodium selenite for 1, 3, and 6 mo. In a general way, percentages of saturated, monounsaturated, and polyunsaturated fatty acids of supplemented groups were not different from those obtained with nontreated animals in the analyzed tissues. However, in rats supplemented with 0.5 ppm Se, mainly in adipose tissue, a polyunsaturated fatty acids increase (p<0.005) was observed for all times of treatment. This could suggest that 0.5 ppm Se supplement probably exercises a protective role on polyunsaturated fatty acids in that tissue. Supplements of 6.0, 15.0, and 54.0 ppm Se did not change unsaturation levels of fatty acids in the analyzed tissues.