Do surface-active lipids in food increase the intestinal permeability to toxic substances and allergenic agents?

The incidence of many common diseases has increased during the last decades. High fat intake is a risk factor for many diseases. We propose that some of the negative effects of fat are caused by lipid-induced damage of the gastrointestinal epithelium, thus compromising the epithelial function as a barrier for passage of toxic substances and allergenic agents to the circulatory system. Monoglycerides (MGs), phospholipids and fatty acids (FAs) are surface-active molecules that in pharmaceutical studies act as permeability enhancers for hydrophilic drugs with low absorption. Three possible mechanisms were proposed: (a) lipid-induced alterations in intracellular events may cause destabilization of tight junctions between the GI epithelial cells, (b) lipids may destabilize cell membranes, (c) lipids cause intestinal cell damage, which increase the permeability of the GI epithelium. These "side effects" of lipids may partly explain the association between fat intake and disease observed in epidemiological studies.

Polychlorinated biphenyl congeners as markers of toxic equivalents of polychlorinated biphenyls, dibenzo-p-dioxins and dibenzofurans in breast milk.

In breast milk, concentrations of polychlorinated biphenyls (PCBs) are higher than those of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), making PCB analyses less time-consuming and expensive. We searched for PCB "markers" of PCDD/DF concentrations, by studying associations between concentrations of PCB and PCDD/DFs (expressed as toxic equivalents, TEQs) in breast milk from 27 women (primiparas, 22-35 years). These women donated breast milk in 1996-1999 together with 183 other primiparas from Uppsala County, Sweden. Regression analyses showed that both dioxin-like and non-dioxin-like penta- to hepta-chlorinated PCBs could be used as markers of TEQ concentrations in this group of women, in some cases after age adjustment of the regressions. The strong positive association between concentrations of dioxin-like PCB/DD/DFs and non-dioxin-like PCBs will in future epidemiological studies make it difficult to separate Ah receptor-dependent effects from non-Ah receptor-dependent effects. With the use of regression equations and concentrations in breast milk samples collected in 1994, TEQ concentrations were estimated in the 1994 samples. Comparisons between estimated and measured concentrations indicated that associations between concentrations of marker substances and TEQs should be determined separately within each study population, in order to obtain reliable TEQ exposure assessments from PCB markers.

The influence of complexing agents on the solubility and absorption of aluminium in rats exposed to aluminium in water.

The influence of citrate (0-31 mM), fluoride (0 or 2.6 mM) and silicate (0 or 2.6 mM) on the absorption of Al (0-18 mM) was studied in rats. We tested the hypothesis that the solubility and absorption of Al increases in the gastrointestinal (GI) tract in the presence of the complexing agents. Male rats were exposed for 6 or 7 weeks to soluble Al in acidic drinking water (pH 2.5-3.0) with or without the complexing agents. At the end of exposure Al was fractionated in the stomach content, in order to study if the solubility of Al was changed after ingestion. Al absorption was estimated by Al analysis of the right femur bone. Speciation calculations indicated that citrate and fluoride caused formation of soluble Al-citrate (97%) and -fluoride (> 60%) complexes in the water. Silicate did not affect the theoretical speciation. In all cases, a large fraction of soluble Al became insoluble in the stomach after ingestion. The concentration of soluble Al increased only in the presence of citrate or a mixture of fluoride and silicate, but citrate was the only complexing agent that influenced the absorption of Al in the rat. This indicates that the form of Al may be changed in the GI tract when soluble drinking-water Al is ingested, and that the solubility of Al in drinking water and GI tract may not be good predictors of the bioavailability of Al even when chelating agents are present.

Cadmium absorption in mice: effects of broiling on bioavailability of cadmium in foods of animal origin.

The absorption and organ distribution of organic Cd from raw and broiled horse kidney was compared to that of CdCl2 at two dose levels (0.05 and 3 mg Cd/kg feed) in a feeding study in mice. The high Cd concentration in the horse kidney (raw 112 mg/kg; broiled 53 mg/kg) made it possible to mix kidney into mouse feed without marked effects on the composition of the feed. The weight of the mice, feed and water consumption, and Cd levels in the feed were determined once a week. After 9 wk of exposure, the liver and kidneys of the mice were sampled and Cd was analyzed. The Cd concentration in horse kidney was halved by broiling, and the content of soluble Cd decreased from 12% in raw kidney to 5% in broiled kidney. The majority of the soluble Cd was associated with proteins with the same molecular weight as metallothionein (MT) in both raw and broiled kidney. Broiling of the kidney had no marked effect on the fractional accumulation of organic Cd in mice. The fractional accumulation of inorganic CdCl2, on the other hand, was significantly higher than that of organic Cd in the low dose groups but not in the high dose groups. The ratio between Cd accumulation in kidney and that in liver was higher in the group receiving raw kidney compared to the ratio in the group receiving CdCl2 at both the high and low exposure levels. This indicates that the raw kidney contained a Cd form that was more preferentially distributed to the kidneys.

PCB and chlorinated pesticide concentrations in swine and bovine adipose tissue in Sweden 1991-1997: spatial and temporal trends.

Results from the Swedish control programme regarding organochlorines in food were used to determine time trends of organochlorine concentrations in adipose tissues from swine (4-8 months old) and bovines (non-dairy, 12-36 months) slaughtered between 1991 and 1997. Moreover, possible regional differences in concentrations were studied, as well as differences in concentrations depending on sex and age of the slaughtered animals. Multiple linear regression indicated that the concentrations of PCB, p,p'-DDE, HCB and alpha-HCH decreased by 4-17% per year, suggesting that the decline in organochlorine concentrations in the Swedish environment and biota reported during the 1970s-1990s also has occurred in meat-producing animals during the 1990s. The concentrations of PCB, DDE and HCB in bovines and PCB and DDE in swine were 1.4-3.8-fold higher in the southern parts of Sweden than in the northern parts of the country, indicating a regional difference in exposure of the animals. The organochlorine concentrations were higher in bovines than in swine, and declined faster in swine than in bovines. Moreover, the concentrations of CB 153 and p,p'-DDE were similar in bovines, but in swine the average concentrations of the two compounds differed two-fold. Apart from possible species differences in metabolism of organochlorines, this may be due to differences in the age at slaughter between swine and bovines, and differences in husbandry of the animals. In the latter case, swine are generally kept inside during their whole life span, whereas bovines are kept outside grazing during the summer period. Finally, a sex-dependent difference in concentrations was indicated in swine, but not in bovines. Our study shows that a lot of information can be 'extracted' from control program results.

Organochlorines and bone mineral density in Swedish men from the general population.

Persistent organochlorines (POCs), such as polychlorinated biphenyls (PCBs) and DDT, are present at relatively high concentrations in food and show estrogenic, anti-estrogenic or anti-androgenic activity in biological test systems. Because bone mineral density (BMD) in men is influenced by sex hormones, we looked for associations between BMD and serum concentrations of POCs in 115 men (mean age 63 years, range 40-75 years) from the general Swedish population. Ten PCB congeners, five DDT isomers, hexachlorobenzene, three hexachlorocyclohexane isomers, trans-nonachlor and oxychlordane were analyzed by gas chromatography. Quantitative bone measurements were performed by dual-energy X-ray absorptiometry at three sites: whole body, the L2-L4 region of the lumbar spine, and the neck region of the proximal femur, as well as by quantitative ultrasound on the left os calcis (broadband ultrasound attenuation (BUA) and speed of sound (SOS)). After adjustment for confounding factors in linear regression analyses we found no strong association between serum concentrations of single POCs and the five BMD and ultrasound variables. When POCs were grouped according to hormonal activity (estrogenic, anti-estrogenic, anti-androgenic) and the study subjects were divided into organochlorine concentration quartiles, a weak association was indicated between increased serum concentrations of p,p'-DDE (antiandrogenic) and decreased BMD, BUA and SOS. This may suggest that p,p'-DDE could cause negative effects on bone density, but the findings might also be due to chance since multiple comparisons were made in the statistical analysis. Overall our results do not suggest that the studied POCs caused major effects on bone density in our study group.

Serum concentrations of organochlorines in men: a search for markers of exposure.

Analysis of single marker substances in serum could provide cost-effective assessment of human exposure to complex mixtures of organochlorines. We studied the serum concentrations of 10 polychlorinated biphenyl (PCB) congeners and 11 chlorinated pesticides and some of their metabolites in samples collected from 120 Swedish men (mean age 63 years, range 40-74 years) from the general Swedish population. The median concentrations of individual PCB congeners increased in the order PCB 52 < PCB 101 < or = PCB28 < PCB 105 < PCB 167 < PCB 156 < PCB 118 < PCB 138 < PCB 180 < PCB 153. The concentrations of o,p'-DDT, o,p'-DDE, p,p'-DDD, alpha-HCH and gamma-HCH were in most cases below the quantification limit (2-4 ng/g lipid). Among the other chlorinated pesticides the median concentration increased in the order oxychlordane (12 ng/g lipid) < p,p'-DDT < trans-nonachlor < beta-HCH < HCB < p,p'-DDE (586 ng/g lipid). The observed concentrations of PCB and chlorinated pesticides were in the same range as those found in similar groups of men from Sweden and Norway, but lower than those found in male populations with recent occupational exposure or high environmental exposure. Strong relationships were found between the concentrations of single mono- and di-ortho PCB congeners and groups of PCB congeners in serum. In our group of men PCB 153 was a good marker substance for the concentration of sigma PCB and sigma di-ortho PCB concentrations in serum. Moreover, among the mono-ortho PCB congeners analyzed, PCB 156 could be used as a marker for the sigma mono-ortho PCB TEQ concentrations in serum in the studied group. No useful marker substances were found among DDT compounds and other chlorinated pesticides and metabolites, except for trans-nonachlor which predicted the concentration of the metabolite oxychlordane fairly well.

Does aluminium stimulate the immune system in male rats after oral exposure?

The influence of oral aluminium exposure on the immune system was studied in rats. Male rats were exposed to soluble and labile Al in acidic drinking water (0-500 mg Al/l) for 7-9 weeks. The concentration of Al in femur bone was higher in rats exposed to 50 and 500 mg Al/l (mean concentration 277 and 599 ng Al/g) than in control rats (150 ng Al/g). The Al concentration in blood plasma could only be quantified in the 500 mg/l group (mean 2.7 ng/ml), whereas the concentrations in the control and 50 mg/l groups were low (< 2 ng Al/ml). Exposure of 4-13-weeks-old rats to the highest Al concentration caused an increased number of splenocytes, whereas exposure of 9-16-weeks-old rats to 500 mg Al/l caused an increased number of thymocytes. Moreover, the proliferative response of splenocytes to the mitogen Con A (2 micrograms/ml) was increased by exposure of the 9-16-weeks-old rats to 500 mg Al/l as compared with the controls. The results indicate that oral Al exposure caused a slight stimulation of some immune functions in the rat at Al plasma concentrations normally found in the human population (< 10 ng Al/ml).

Intestinal absorption of copper from drinking water containing fulvic acids and an infant formula mixture studied in a suckling rat model.

The purpose of this study was to investigate if the intestinal absorption of copper in drinking water is altered in the presence of complexing agents from a fulvic acid mixture and an infant formula powder. Ten to twelve day old rat pups were given a single oral dose of radio-labeled Cu in deionized water (0.93 mg Cu/l), in water containing fulvic acids (10 mg/l), in infant formula mixed with deionized water, or in infant formula mixed with water containing fulvic acids. Six hours after dosage, radioactive Cu was analyzed in the mucosa of the small intestine, the liver and the remaining carcass (excluding the liver and gastrointestinal tract) by gamma counting. Dialysis and centrifugation experiments showed that Cu was complexed by components in the fulvic acid and formula mixtures, although the presence of fulvic acids in the water did not alter the Cu fractionation in the formula. The fractional Cu uptake (% of dose) from the intestinal lumen to the mucosa was not markedly changed by the presence of the chelating agents. However, the retention of Cu in the intestinal mucosa was increased by both fulvic acids and formula. Concomitantly, the absorption rate of Cd to the circulatory system was decreased. No interactive effect between fulvic acids and formula was found on the Cu absorption. These findings indicate that the water quality may be an important determinant of the rate of intestinal Cu absorption from drinking water. Moreover, in the future risk assessment of copper in drinking water, the possibility of alterations in absorption of drinking-water Cu has to be considered when the drinking water is used for cooking.

The influence of humic substances on the absorption and distribution of cadmium in mice.

The complex binding of cadmium ions to humic and fulvic acids in water may influence the absorption and distribution of drinking-water Cd in humans. Thus, in the present study mice were given a single oral dose of Cd (109CdCl2, 25 microg/l) in 100 microl Millipore water containing different concentrations of humic compounds (0, 1, 10 and 100 mg dissolved organic carbon/l). The complex binding of Cd was studied by dialysis. At neutral pH, 1 mg dissolved organic carbon/l caused complex binding of more than 50% of the Cd, whereas more than 90% of Cd was bound at 10 and 100 mg dissolved organic carbon/l. At pH 3 the complex binding of Cd decreased somewhat, but over 90% of the Cd was bound at 100 mg dissolved organic carbon/l. Complex binding of Cd increased the lipid solubility of Cd, expressed as an octanol/ water partition coefficient, Nevertheless, more than 99% of the bound Cd was present as hydrophilic binding forms. Irrespective of the bound of Cd, the intestinal uptake and intracellular distribution (gel filtration on Sephadex G-75 column) were not affected by the humic substances 6 hr after dosage. Moreover, complex binding did not influence the intestinal absorption of Cd 24 hr after exposure. The median Cd retention in the kidneys of the 100 mg dissolved organic carbon/l group was 23% and 46% lower than that of the control group 6 and 24 hr after administration, respectively, indicating alterations in the distribution of Cd after absorption. Thus humic substances may affect the metabolism of toxic heavy metals, such as Cd, in vivo in mice, indicating that the presence of humic and fulvic acids in drinking water should be considered in future risk assessments of metals in drinking water.

Concentration-dependent absorption of aluminum in rats exposed to labile aluminum in drinking water.

The hypothesis was tested that the absorption of labile Al in rats will increase when the Al-binding capacity of food components in the stomach is saturated. Male rats were exposed to 0, 10, 50, or 500 mg labile Al/L in acidic drinking water (pH 3) for 9 wk. The results show that labile Al in drinking water is complexed by feed constituents in the stomach of the rat in vivo, thus causing a nondetectable absorption of Al at 10 mg Al/L. An increased absorption of Al at 50 and 500 mg Al/L was associated with a saturation of the Al-binding capacity of feed components in the lumen of the stomach, causing the appearance of labile Al. Thus, the presence of labile Al in drinking water does not necessarily result in a high Al absorption when the water is ingested, since the bioavailability of labile Al is dependent both on the amount and composition of Al-binding components present in the gastrointestinal tract at the time of ingestion of the water. It is thus not possible to predict the body burden of Al in humans just by measuring the Al concentrations in drinking water. Even a further refining of the exposure measurement to include speciation of Al in the water may not markedly improve the prediction of the Al body burden. Future epidemiological studies must therefore be based on actual measurements of Al concentration in tissues or fluids from the study subjects.

Accumulation of cadmium from wheat bran, sugar-beet fibre, carrots and cadmium chloride in the liver and kidneys of mice.

The gastrointestinal absorption and organ distribution of Cd after exposure for 9 weeks to three fibre-rich foodstuffs (wheat bran, sugar-beet fibre and carrots) were determined in mice. Groups of eight mice were given a diet containing 0.05 mg Cd/kg from wheat bran, sugar-beet fibre, carrots or CdCl2 mixed in a semi-synthetic, low-Cd (< 0.007 mg/kg) feed. A control group was fed on the low-Cd semi-synthetic feed. The water consumption, food consumption and the weight of the animals were monitored throughout the study. The feed was changed once weekly and Cd was analysed in the feed at each change. myo-Inositol phosphates (hexa-, penta-, tetra- and tri-) and Zn, Cu, Fe and Ca were also analysed in the diets. After 9 weeks, the mice were killed and liver and kidneys were sampled and analysed for Cd. The group receiving the wheat-bran diet had significantly lower fractional Cd accumulation (% total Cd intake) in the liver and kidneys than the other groups, indicating a lower fractional absorption of Cd. The wheat-bran diet had markedly higher levels of inositol hexa- and pentaphosphates (phytates) and a Zn level that was twice as high as those in the other diets. The higher levels of myo-inositol hexa- and pentaphosphates in the wheat-bran diet most probably contributed more to the lower fractional absorption of Cd than the elevated Zn level, due to the formation of insoluble Cd-phytate complexes. Compared with the wheat-bran diet, the sugar-beet-fibre and carrot diets contained very low levels of myo-inositol penta- and hexaphosphates, and consequently the fractional Cd absorption from these diets was higher.

The intestinal absorption of cadmium increases during a common viral infection (coxsackie virus B3) in mice.

Murine intestinal absorption, tissue accumulation and redistribution of 109Cd during infection were studied using the common human virus Coxsackie virus B3 (CB3) adapted to the mouse. Female Balb/c mice were infected with CB3 and, on day 4 of the infection, dosed orally with 0.3 or 750 microgram Cd/kg body weight, with 109Cd as a tracer, in order to study intestinal absorption and tissue distribution of Cd during infection (Experiment 1). Other mice were dosed with 0.3 microgram Cd/kg body weight 3 days before being infected and, on day 4 of the infection, Cd redistribution was studied (Experiment 2). In both experiments non-infected control animals received the same treatment as infected animals. Results showed that the infected animals had a higher gastrointestinal absorption of Cd than noninfected animals when Cd was administered during infection. In the infected animals the absorption at the low Cd dosage was increased by 70% and was tripled at the high dosage. The increased absorption enhanced the accumulation of Cd in all organs studied. Moreover, the infection caused a Cd dose-dependent change in the organ distribution of Cd, when Cd was administered during the infection. However, no redistribution of previously accumulated Cd occurred during ongoing disease, indicating that Cd was not mobilised from body stores by the infection. These results show, for the first time, that an invading micro-organism can increase the intestinal absorption and concomitantly alter the tissue distribution of an environmental pollutant (Cd) if exposure occurs during the course of viral infection.

Cadmium accumulation in liver and kidney of mice exposed to the same weekly cadmium dose continuously or once a week.

Cd levels in blood, liver and kidney of female mice were measured after exposure to Cd as CdCl2 in the food, either continuously (CE group) throughout the week (300 microg Cd/kg feed) or for 24 hr/wk (2100 microg Cd/kg) for 5 wk (occasionally exposed, OE group). In a control group that received feed with Cd levels below the detection limit (< 7 microg/kg), Cd levels in blood, liver and kidneys were below the detection limit after the 5 wk of exposure. The weekly dose of Cd administered to the exposed CE and OE groups was similar (approx. 400 microg Cd/kg mice/wk). The OE group had a higher Cd level in blood and a higher fractional accumulation (% of dose) of Cd in the liver and kidneys compared with the CE group. This indicates that the fractional Cd absorption in the gastrointestinal tract is higher when high Cd doses are ingested occasionally than when low doses are ingested continuously, even if weekly doses are the same. It is hypothesized that this difference in absorption could be due to Cd-induced unspecific damage to the intestinal mucosa, changes in tight-junction permeability caused by Cd, or to a saturation of the Cd-binding capacity of the intestinal mucosa in mice exposed to high Cd levels occasionally.

Influence of water quality on the accumulation of methyl 203mercury in gill tissue of minnow (Phoxinus phoxinus).

Effects of pH and concentrations of Cl and Ca on the uptake of methyl mercury (MeHg) in the gills of the minnow (Phoxinus phoxinus) were studied. Chloride concentration and pH in the water affect the speciation of MeHg. Ca was included because it affects the permeability of the gills and could therefore indirectly affect the amount of MeHg accumulated in the tissue. The species formed differ in hydrophobicity, as reflected in their octanol/water partition coefficients (Pow). Both a reduction in pH and an increase in Cl- concentration increased the Pow of MeHg. Ca had no effect on speciation. The accumulation of MeHg in the gill tissue increased with decreasing pH (from pH 7.0 to pH 3.9). Accumulation also increased as Cl- concentrations were increased from 10(-7) to 10(-1) M at pH 7.0. An increase in Ca concentration did not alter the accumulation of MeHg beyond a decrease in MeHg accumulation as Ca increased from 20 to 50 microM. We conclude that, of the water-quality factors studied, those affecting chemical speciation were most important in determining the MeHg uptake. The Ca concentration appears to be of minor importance.

Effect of long-term sodium selenite supplementation on levels and distribution of mercury in blood, brain and kidneys of methyl mercury-exposed female mice.

Female Balb/c CA mice were supplemented for seven weeks with 0, 0.6 and 3 p.p.m. Se in tap water and were then exposed to a single oral dose of Me203Hg (2 mumol/kg). Se supplementation continued for 56 days after MeHg dosage. Supplemented animals showed enhanced activity of glutathione peroxidase in the blood. Twenty-four hr after MeHg dosage, the level and distribution of Hg in blood, blood cells, and kidneys were not influenced by Se exposure. However, in the brain the Hg accumulation was increased and Hg distribution was altered by Se supplementation. Fifty-six days after MeHg dosage, 70% to 80% of the dose had been eliminated from the body, and the brain of the 3 p.p.m. group still had a higher Hg level than the control group. Otherwise, there was no consistent effect of Se supplementation on retention of Hg in the animals. It is indicated that Se influences tissue accumulation and intracellular distribution of Hg through tissue-specific mechanisms rather than through a more general effect on Hg sequestration and transport in the blood.

Aluminium fractionation in a simulated rat stomach: an in vitro study.

This study is part of a project dealing with the absorption of aluminium in rats from acidified drinking water. The hypothesis of the project was that 'labile' forms of aluminium in water might be more available for absorption than aluminium in food. To investigate this hypothesis, the distribution of species of the metal within the rat stomach must be considered. So far, few attempts in this direction have been made. The distribution of aluminium forms in vitro was studied, simulating the conditions present in a rat stomach. The in vitro set-up is based on methods used for drug release studies. The results show that only part of the aluminium (29-54%) added in 'labile' forms at a concentration of 4.0 mg l-1 Al was detected as total dissolved aluminium (Altot) after incubation in a simulated rat stomach. The levels of 'quickly reacting aluminium' (Alqr) (approximately the sum of Al and its monomeric hydroxo and sulfato complexes) were very low (< 0.2 mg l-1), but difficult to quantify precisely in this matrix. The pattern of the in vitro results was confirmed by measurements in pooled rat stomachs from in vivo experiments. There are obviously considerable amounts of ligands present in rat feed that bind strongly to aluminium and thereby affect the distribution of metal species inside the rat stomach. It is believed that phosphoserine, present in the protein casein, is an important ligand for aluminium complexation in this case. The results show that studies of Al absorption should be accompanied by fractionation measurements within simulated or real gastric systems.

Fulvic and humic acids decrease the absorption of cadmium in the rat intestine.

Dissolved organic carbon (DOC) in drinking water is mainly composed of fulvic and humic acids, which may form complexes with metal ions. The influence of DOC on the intestinal absorption of Cd in the rat was investigated using an "isolated intestinal segment" technique in anaesthetised rats. The lumens of segments were exposed for 60 min to different concentrations of CdCl2 and DOC in intact animals. The fractional absorption (FA) was not dose dependent in the dosage interval 0.01-0.03 microgram Cd/kg. However, at 15 and 150 micrograms Cd/kg both FA and intracellular Cd distribution in the segments were dose dependent, which is in line with results from other studies performed on similar experimental models. In the presence of 1 and 10 mg DOC/l, FA of Cd was just half as high as FA in animals that received Cd alone (0.01 microgram/kg). Moreover, a higher percentage of Cd was associated with the metallothionein fraction in the intestinal segment of the DOC-dosed rats. An in vitro speciation experiment showed that only 0.2-7.9% of the Cd in the incubation solution was complexed to DOC. In deionized water, however, more than 99% of the Cd was complexed to DOC. This result indicates that the incubation solution contained substances that negatively affect complexation of Cd to DOC. Mechanisms other than complexation of Cd to DOC in the intestinal lumen may therefore be involved in the inhibitory effect of DOC on the absorption of Cd.

Influence of sodium selenite on 203Hg absorption, distribution, and elimination in male mice exposed to methyl203Hg.

To study the effects of long-term selenium supplementation on absorption, distribution, and elimination of methylmercury (MeHg) in mice, three groups of male mice (Balb/c CA) were exposed for 7 wk to 0, 0.6, and 3 ppm sodium selenite in tap water. They were then given a single oral dose of Me203Hg (2 mumol/kg) by gastric intubation, and elimination of 203Hg was followed by whole-body counting for 49 d at the same Se exposure as previously. Twenty-four hours and 49 d after dosage, 6-7 animals/group were sampled for analysis of 203Hg distribution in the body. Glutathione peroxidase (GSH-PX) activity in blood and selenium levels in the liver were used as measures of selenium status. Gastrointestinal absorption of Me203Hg was not influenced by the Se status of the animals. Selenium supplementation of MeHg-exposed mice caused an enhanced whole-body elimination of Hg, but selenium-supplemented animals did not have lower Hg levels in the brain and kidney than nonsupplemented animals. The effect of selenium on the accumulation of Hg in the brain was dose-dependent, a high dose (3 ppm Se) causing a higher initial accumulation of Hg. The intracellular distribution of 203Hg in the liver and kidney was not affected by Se. The results indicate that selenium treatment of MeHg-exposed mice may have a positive effect on the health of the animals by decreasing the total body burden of MeHg.

Altered distribution of 109cadmium in mice during viral infection.

The distribution of the toxic heavy metal cadmium (Cd) was studied in Coxsackie virus B3 (CB3)-infected Balb/c mice by whole-body autoradiography and gamma-counting. The distribution of 109Cd was studied 4 days post CB3-inoculation and 10 min after intravenous injection of 0.21 microgram of Cd/kg body weight. Whole-body autoradiography results showed that the distribution of 109Cd is greatly changed during this viral infection. This newly discovered distribution was mainly visible as a greatly increased accumulation in the renal and adrenal cortices. After impulse counting of selected organs it was found that the normal accumulation of 109Cd in the kidneys (184,354 +/- 30,961 c.p.m.) was increased by 47% (P less than 0.05) during CB3 infection (270,503 +/- 54,780 c.p.m.). In contrast to healthy animals, some infected mice showed accumulation of 109Cd in the spleen. These results show for the first time that an invading micro-organism can change the distribution of an environmental pollutant.