Arsenic possibly influences carcinogenesis by affecting arginine and zinc metabolism

The role of arsenic in carcinogenesis is controversial. There is no doubt arsenic can influence carcinogenesis under certain conditions. However, a review of the findings relating arsenic to cancer indicates that arsenic mainly affects carcinogenesis indirectly by influencing other metabolic systems (i.e., immune system) or nutrients (i.e., arginine, zinc) that may have a more direct role in the carcinogenic process. Depending upon the level of exposure, arsenic can either inhibit or activate interferon, an inhibitor of virus replication. Furthermore, arsenic can apparently inhibit some virusinduced tumorigenesis. However, once a tumor is initiated, arsenic enhances tumor growth, possibly by affecting the immune response. Recent experiments in our laboratory demonstrated that arsenic metabolically interacts with arginine and zinc, both of which apparently influence the immune response. Arsenic evidently has a role that strongly influences the metabolism of arginine, which is an immunostimulatory amino acid. Furthermore, the effect of arsenic on arginine metabolism is apparently modified by the zinc status of the animal. Because arsenic can apparently affect cancer development through several indirect or direct mechanisms, probably the only general conclusion that can be made about arsenic and cancer is that arsenic, depending upon dosage, route of administration, and chemical form, modifies the induction or development of some tumors.     

Effect of nitrous oxide on nickel deprivation in rats

Because nickel may have a biological function in a pathway in which vitamin B₁₂ is important, an experiment was performed to determine the effects of nitrous oxide exposure in rats deprived of nickel. Exposure to nitrous oxide (N₂O) causes inactivation of cobalamin and a subsequent decrease in the vitamin B₁₂-dependent enzymes methionine synthase and methylmalonyl CoA mutase. Rats were assigned to dietary groups of 12 in a factorially arranged experiment with dietary variables of nickel (0 or 1 μg/g) and vitamin B₁₂ (0 or 50 ng/g). After 6 wk, one-half of the rats from each dietary group were exposed to 50% N₂O/50% O₂ for 90 min/d for the last 28 d of the experiment. Vitamin B₁₂, N₂O, or their interaction had numerous effects; classical findings included N₂O-induced reduction in plasma vitamin B₁₂ and decreases in the vitamin B₁₂-dependent enzymes. Inactivation of vitamin B₁₂ by N₂O, however, did not exacerbate signs of nickel deprivation, possibly because the rats were able to metabolically compensate to N₂O exposure. Mention of a trademark or proprietary product in this article does not constitute a guarantee or warranty of the product by the United States Department of Agriculture and does not imply its approval to the exclusion of other products that may also be suitable.     

Trophic state and nutrient limitation in Lake Baringo,Kenya

The trophic state of Lake Baringo and factors that could be limiting the development of algal biomass in it were investigated during one wet/dry hydrological cycle in 2014–2015. Water samples were analysed for dissolved inorganic nutrients, including , and , total phosphorus and Chlorophyll a. Light attenuation was estimated using Secchi depth. The trophic state was determined using Carlson trophic state indices (CTSI). Deviations in CTSI, nutrient ratios and ambient nutrient concentrations were used to identify factors limiting phytoplankton growth. The mean values measured for Secchi depth, nitrate, total phosphorus and Chlorophyll a showed significant seasonal variation (p < 0.05). Based on the Carlson trophic state index, the results show that Lake Baringo is eutrophic. However, the lake is also experiencing phosphorus limitation and poor light penetration, because of high turbidity, which is more pronounced during the wet season.     

Specific activity of methionine sulfoxide reductase in CD-1 mice is significantly affected by dietary selenium but not zinc

Reactive oxygen species-mediated oxidation of methionine residues in protein results in a racemic mixture of R and S forms of methionine sulfoxide (MetO). MetO is reduced back to methionine by the methionine sulfoxide reductases MsrA and MsrB. MsrA is specific toward the S form and MsrB is specific toward the R form of MetO. MsrB is a selenoprotein reported to contain zinc (Zn). To determine the effects of dietary selenium (Se) and Zn on Msr activity, CD-1 mice (N=16/group) were fed, in a 2×2 design, diets containing 0 or 0.2 μg Se/g and 3 or 15 ∥ Zn/g. As an oxidative stress, half of the mice received L-buthionine sulfoximine (BSO; ip; 2 mmol/kg, three times per week for the last 3 wk); the others received saline. After 9.5 wk, Msr (the combined specific activities of MsrA and MsrB) was measured in the brain, kidney, and liver. Se deficiency decreased (p<0.0001) Msr in all three tissues, but Zn had no direct effect. BSO treatment was expected to result in increased Msr activity; this was not seen. Additionally, we found that the ratio of MetO to methionine in liver protein was increased (indicative of oxidative damage) by Se deficiency. The results show that Se deficiency increases oxidation of methionyl residues in protein, that Se status affects Msr (most likely through effects on the selenoprotein MsrB), and that marginal Zn deficiency has little effect on Msr in liver and kidney. Finally, the results show that the oxidative effects of limited BSO treatment did not upregulate Msr activity.     

Toxic effects of copper sulfate on the brains of term Hubbard broiler chicks: a stereological and biochemical study

Copper sulfate can cause different pathologies in different organ systems during development. We determined the effects of toxic levels of copper sulfate on brain development in term Hubbard broiler chicks using stereological and biochemical analyses. Hubbard broiler chicken eggs were divided into three groups: controls with no treatment, sham-treated animals and an experimental group. On day 1, 0.1 ml saline was injected into the air chambers of the sham and experimental groups. The experimental group received also 50 μg copper sulfate. At term (day 21), all chick brains were removed and their volumes were determined using the Cavalieri volume estimation. Parallel biochemical analyses were carried out for glutathione and malondialdehyde levels in the brain tissues as indicators of oxidative damage. With copper treatment, the mean brain volume (8079 μm³) was significantly decreased compared to both the control (10075 μm³) and sham (9547 μm³) groups. Copper treatment (143.8 nmol/g tissue) showed significantly decreased malondialdehyde levels compared to the control (293.6 nmol/g tissue) and sham groups (268.8 nmol/g tissue). Copper treatment (404.5 nmol/g tissue) showed significantly increased malondialdehyde levels compared to the control (158.6 nmol/g tissue) and sham (142.8 nmol/g tissue) groups. The morphological and biochemical parameters we measured demonstrated that in term Hubbard broiler chicks, toxic levels of copper sulfate cause developmental and oxidative brain damage.     

Interaction between zinc and iron in rats

The importance of interactive effects, of minerals in general, on nutrient requirements is becoming increasingly recognized. The interaction between iron and zinc has not been as widely investigated. The metabolic interrelationships between dietary iron and zinc have been known for years, but some subtle relationships may have gone unrecognized. Because nutrient interactions are not necessarily linear in nature, it may be inadequate to apply linear statistical models to study the interaction between zinc and iron. In this study, we used traditional as well as a nonlinear approach in analyzing experimental results from groups of rats fed a wide range of dietary zinc and iron. Male weanling Sprague-Dawley rats were used in a 5 × 4 factorially arranged experiment. Dietary variables were iron (as ferric citrate) at 4, 12, 24, 48, or 96 μg Fe/g diet and zinc (as zinc carbonate) at 5, 10, 20, or 40 μg Zn/g diet. After 7 wk, hematological parameters were measured and plasma ceruloplasmin and cholesterol were determined. In addition to interactive effects as shown by analysis of variance, the application of log-linear analysis to the experimental data revealed a far broader range of interactions between dietary iron and zinc. As a result of our experiment and its quantitative analysis, we conclude that the interaction between iron and zinc is nutritionally important and that dietary iron affected the response of many blood parameters to dietary zinc. The complete dataset can be found at http://www.gfhnrc.ars.usda.gov/fezn. U.S. Department of Agriculture, Agricultural Research Service, Northern Plains Area is an equal opportunity/affirmative action employer and all agency services are available without discrimination.     

Magnesium and methionine deprivation affect the response of rats to boron deprivation

A series of nine experiments were done to obtain further evidence that boron might be involved in major mineral metabolism (Ca, P, and Mg), thus indicating that boron is an essential nutrient for animals. Eight factorially arranged experiments of 6–10 wk durations were done with weanling Sprague-Dawley male rats. One factorially arranged experiment was done with weanling spontaneously hypertensive rats. The variables in each experiment were dietary boron supplements of 0 and 3 μg/g, and dietary magnesium supplements of either 200 (Experiments 1–3) or 100 (Experiments 4–9) and 400 μg/g. In Experiments 7 and 9, a third variable was dietary manganese supplements of 25 and 50 μg/g. Methionine status was varied throughout the series of experiments by supplementing the casein-based diet with methionine and arginine. Findings were obtained indicating that the severity of magnesium deprivation and the methionine status of the rat strongly influence the extent and nature of the interaction between magnesium and boron, and the response to boron deprivation. When magnesium deprivation was severe enough to cause typical signs of deficiency, a significant interaction between boron and magnesium was found. Generally, the interaction was characterized by the deprivation of one of the elements making the deficiency signs of the other more marked. The interaction was most evident when the diet was not supplemented with methionine and especially when the diet contained luxuriant arginine. Signs of boron deprivation were also more marked and consistent when the diet contained marginal methionine and luxuriant arginine. Among the signs of boron deprivation exhibited by rats fed marginal methionine were depressed growth and bone magnesium concentration, and elevated spleen wt/body wt and kidney wt/body wt ratios. Because the boron supplement of 3 μg/g did not make the dietary intake of this element unusual, it seems likely that the response of the rats to dietary boron in the present study were manifestations of physiological, not pharmacological, actions, and support the hypothesis that boron is an essential nutrient for the rat. Mentions of a trademark or proprietary product does not consitute a guarantee or warranty of the product by the US Department of Agriculture and does not imply its approval to the exclusion of other products that may also be suitable.     

Diethyl maleate,an in vivo chemical depletor of glutathione,affects the response of male and female rats to arsenic deprivation

An experiment was performed to determine the effect of diethyl maleate (DEM), and in vivo depletor of glutathione, on the response of male and female rats to arsenic deprivation. A 2×2×2 factorially arranged experiment used groups of six weanling Sprague-Dawley rats. Dietary variables were arsenic at 0 or 0.5 μg/g and DEM at 0 or 0.25%; the third variable was gender. Animals were fed for 10 wk a casein-ground corn based diet that contained amounts of calcium, phosphorus, and magnesium similar to the AIN-76 diet. DEM supplementation increased blood arsenic in both male and female rats; female rats had the greatest amount of arsenic in whole blood. Although female rats in general had a lower concentration of glutathione in liver, those fed no supplemental DEM, regardless of their arsenic status, had the lowest amounts. Compared to males, female rats had a lower activity of liver glutathione S-transferase (GST). Arsenic deprivation decreased, and DEM supplementation increased liver GST activity in both male and female rats. Lung GST activity was also increased by DEM supplementation in male, but not female, rats. The most striking finding of the study was that compared to males, females had extremely elevated kidney calcium concentrations, and that the elevation was exacerbated by arsenic deprivation. DEM supplementation also exacerbated the accumulation of calcium in the kidney of the female rats. The response of the rat to both DEM and arsenic was, for many variables, dependent on gender. This gender dependence may be explained by the differences in methionine metabolism between male and female rats. Thus, arsenic deprivation apparently can manifest itself differently depending on gender.