Effect of sodium diethyldithiocarbamate on placental passage and foetal distribution of cadmium and mercury in mice

The administration of sodium diethyldithiocarbamate to 18 day pregnant mice, which previously had been given 109Cd2+ or 203Hg2+ was found to result in increased levels of the metals in the foetuses, in comparison with mice given the 109Cd2+ or 203Hg2+ alone. The level of 109Cd2+ in some foetal tissues was increased 30-60 times. In the animals given 203Hg2+ 3-5 times higher concentrations were seen in most foetal tissues of the sodium diethyldithiocarbamate-treated animals compared with animals not treated with this substance. Cadmium and mercury were shown to form highly lipophilic complexes with diethyldithiocarbamate and a facilitated transfer of these complexes through the placental membranes probably explains the increased uptake of the metals in the foetuses.     

Axonal Transport of Cadmium in the Olfactory Nerve of the Pike

¹⁰⁹Cd²⁺ was applied in the olfactory chambers of pikes (Esox lucius) and the dynamics of the axoplasmic flow of the metal was determined in the olfactory nerves by gamma spectrometry and autoradiography. The results showed that the ¹⁰⁹Cd²⁺ is transported at a constant rate along the olfactory nerves. The profile of the ¹⁰⁹Cd²⁺ in the nerves showed a wave front of transported metal followed by a saddle region. When the nasal chambers were washed 2 hr after application of the ¹⁰⁹Cd²⁺ well-defined transport peaks for the metal were seen in the olfactory axons. The maximal velocity for the transport of ¹⁰⁹Cd²⁺, which corresponds to the movement of the wave front, was 2.38±0.10 mm hr (mean±S.E.) at the experimental temperature (10 C). The average velocity for the transport of the ¹⁰⁹Cd²⁺, which corresponds to the peak apex movement of the wave, was 2.18±0.05 mm/hr (mean±S.E.) at 10 C. The transported ¹⁰⁹Cd²⁺ was strongly accumulated in the anterior parts of the olfactory bulbs, whereas in other brain areas the levels of the metal remained low. Autoradiography of a pike exposed to ¹⁰⁹Cd²⁺ via the water showed a strong labelling in the receptor-cell-containing olfactory rosettes, whereas other structures in the olfactory chambers were only weakly labelled. The accumulation and axonal transport in the olfactory neurons may be noxious and constitute an important component in the toxicology of cadmium in fish, and this may apply also to some other heavy metals.     

Effect of potassium ethylxanthate and sodium diethyldithiocarbamate on the accumulation and disposition of nickel in the brown trout (Salmo trutta)

Brown trouts, Salmo trutta, were exposed to water containing 0.1 or 10 micrograms/l of 63Ni2+, alone or with potassium ethylxanthate or sodium diethyldithiocarbamate. After one and three weeks the accumulation and disposition of the 63Ni2+ in the fish were examined by liquid scintillation spectrometry and whole-body autoradiography. The sodium diethyldithiocarbamate was found to greatly enhance the uptake of 63Ni2+ in several tissues of the trouts. Potassium ethylxanthate was without effect. Diethyldithiocarbamate is known to form lipophilic complexes with metals, including nickel, and a facilitated penetration of the complexed nickel over the cellular membranes of the gills and other tissues is a likely mechanism underlying our results. The ethylxanthate is also able to form a lipophilic nickel-chelate, although of a lower lipophilicity than the nickel-diethyldithiocarbamate-complex. This variance in lipophilicity may explain why the disposition of the 63Ni2+ was affected by the diethyldithiocarbamate, but not by the ethylxanthate.     

Effects of Some Chelating Agents on the Uptake and Distribution of 54Mn(II) in the Brown Trout (Salmo trutta)

The effects of humic acids, which are natural metal-complexing compounds, and potassium ethylxanthate, sodium diethyldithiophosphate, sodium dimethyldithiocarbamate, and sodium diethyldithiocarbamate, which are sulphur-containing man-made chelating agents, on the uptake and tissue distribution of ⁵⁴Mn(II) were studied in brown trout (Salmo trutta). Fish were exposed for 7 days to 0.1 μg Mn(II) · 1^?1 as MnCl₂ (1 μCi ⁵⁴Mn · l^?1) with or without chelating agents. Examination of the partition of Mn between octanol and a Tris-HCl buffer in the presence of these compounds was also performed. Humic acids had only small effects on Mn uptake and distribution in trout, probably because of the low stability of Mn-humate complexes. Partition of Mn in the presence of potassium ethylxanthate, sodium diethyldithiophosphate, sodium dimethyldithiocarbamate, and sodium diethyldithiocarbamate between octanol and Tris-HCl buffer showed formation of lipophilic complex with the latter two compounds, but not with the former. However, these four chelating agents all decreased Mn uptake in the trout by 40-45%. These substances also changed the distribution of Mn within the fish, with a higher proportion of the metal being present in some visceral organs and a smaller proportion being localized in some non-parenchymateous tissues, such as skin, fins and bones. The mechanisms underlying these effects are not known. However, the interaction of chelating agents with the Mn, although weak, may have partially withdrawn the metal from the uptake process in the gills. The redistribution of Mn in the fish may be due to the binding of the metal to complexing compounds which have reached the intestinal lumen. Previous studies with other metals have shown increased or unchanged metal levels in tissues of fish at exposure together with potassium ethylxanthate, sodium diethyldithiophosphate, sodium dimethyldithiocarbamate, and sodium diethyldithiocarbamate, but decreased metal levels have not been observed before.     

Effect of sodium pyridinethione on the uptake and distribution of nickel in rats,ferrets and guinea-pigs

Oral administration of sodium pyridinethione together with Ni²⁺ (using ⁶³Ni²⁺ as a tracer) to rats, ferrets and guinea-pigs produced highly increased tissue levels of the metal in several tissues in comparison with animals given the Ni²⁺ alone. Ni²⁺ forms a lipophilic complex with pyridinethione and it can be assumed that a facilitated passage of the Ni²⁺ across the cellular membranes of various tissues is important for the observed effects. Pigmented tissues (e. g. the eye melanin), the pancreatic islets, the nervous system and striated muscles showed high levels of Ni²⁺ in animals given sodium pyridinethione. However, in some instances marked species differences were observed. Thus, microautoradiography indicated an uptake of Ni²⁺ both in the β- and α-cells in the pancreatic islets in the rat, whereas in the guinea-pig only some cells (probably the α-cells) accumulated high levels of Ni²⁺. In the ferret sodium pyridinethione induced a high uptake of Ni²⁺ in the heart muscle, which was not seen in the other species. The Ni²⁺ is probably taken up in the various tissues complexed to pyridinethione. Within the tissues the complex may dissociate and the Ni²⁺ may bind to some endogeneous tissue components. The affinity of the Ni²⁺ for the endogeneous ligands in relation to the affinity for the pyridinethione may be of importance for the effects on the disposition of the Ni²⁺. The species variations may be related to differences in the structural conformations of the endogeneous Ni²⁺-binding ligands. Received: 25 October 1993/Accepted: 25 January 1994     

Uptake of Manganese and Cadmium from the Nasal Mucosa into the Central Nervous System via Olfactory Pathways in Rats *

Abstract: In the olfactory epithelium the primary olfactory neurones are in contact with the environment and via the axonal projections they are also connected to the olfactory bulbs of the brain. Therefore, the primary olfactory neurones provide a pathway by which foreign materials may gain access to the brain. In the present study we used autoradiography and gamma spectrometry to show that intranasal instillation of manganese (⁵⁴Mn²⁺) in rats results in initial uptake of the metal in the olfactory bulbs. The metal was then seen to migrate via secondary and tertiary olfactory pathways and via further connections into most parts of the brain and also to the spinal cord. Intranasal instillation of cadmium (¹⁰⁹Cd²⁺) resulted in uptake of the metal in the anterior parts of the olfactory bulbs but not in other areas of the brain. This indicates that this metal is unable to pass the synapses between the primary and secondary olfactory neurones in the bulbs. Intraperitoneal administration of ⁵⁴Mn²⁺ or ¹⁰⁹Cd²⁺ showed low uptake of the metals in the olfactory bulbs, an uptake not different from the rest of the brain. Manganese is a neurotoxic metal which in man can induce an extrapyramidal motor system dysfunction associated with occupational inhalation of manganese-containing dusts or fumes. We propose that the neurotoxicity of inhaled manganese is related to an uptake of the metal into the brain via the olfactory pathways. In this way manganese can circumvent the blood-brain barrier and gain direct access to the central nervous system.     

Mobilization of nickel by potassium ethylxanthate in mice: comparison with sodium diethyldithiocarbamate and effect of intravenous versus oral administration

Intravenous administration of 63Ni2+ (as 63NiCl2) together with potassium ethylxanthate resulted in highly increased levels of 63Ni2+ in several tissues of mice in comparison with animals given 63Ni2+ alone. However, this effect was not observed when 63Ni2+ and potassium ethylxanthate were given orally. Sodium diethyldithiocarbamate was active in increasing 63Ni2+ concentrations after both intravenous and oral administration. Both ethylxanthate and diethyldithiocarbamate can form highly lipophilic complexes with nickel and a facilitated penetration of these complexes through the cellular membranes of the tissues probably explains the increased uptake of the metal. Xanthates are unstable at acid pH and degradation in the acid milieu of the stomach probably underlies the lack of effect at oral administration.     

Effects of sodium pyridinethione on the uptake and distribution of nickel, cadmium and zinc in pregnant and non-pregnant mice

Oral administration of sodium pyridinethione together with 63Ni2+, 109Cd2+ or 65Zn2+ to non-pregnant mice resulted in very markedly increased levels of the metals in several tissues in comparison with animals given the metals alone. For 63Ni2+ the sodium pyridinethione induced a strong labelling of the pancreatic islets and of the melanin of pigmented tissues. A considerable radioactivity was also obtained in the peripheral and central nervous system. For 109Cd2+ a strong radioactivity was observed in the red pulp of the spleen and the neurohypophysis and, in addition, in the liver and the kidney. For 65Zn2+ the distribution pictures in mice given 65Zn2+ only were similar to those seen in mice given the metal together with sodium pyridinethione, although the radioactivity in all tissues of the latter animals was much higher than in the former. All 3 metals were shown to form lipophilic complexes with pyridinethione (the nickel and zinc complexes being more lipophilic than the cadmium complex) and a facilitated penetration of the complexed metals through the cellular membranes is probably important for the observed results. Differences in the stability of the complexes in the body may be one factor of importance for the marked differences in the obtained distribution pictures but other factors may also be involved, as discussed in the paper. Experiments in pregnant mice showed markedly increased levels of 63Ni2+ and 65Zn2+ in the foetuses as a result of the sodium pyridinethione administration, whereas for 109Cd2+ only a small increase was observed. Our results suggest that effects on the disposition of metals may be important for the toxicity of the pyridinethiones.     

In vitro and in vivo effects of cadmium on cholinesterases in Nile tilapia fingerlings: implications for biomonitoring aquatic pollution

Effects of cadmium on in vitro and in vivo cholinesterase (ChE) activities of brain and muscle tissues of Oreochromis niloticus fingerlings were evaluated, considering its potential use in biomonitoring tropical water pollution. Results show that in vitro ChE activities were depressed significantly by millimolar concentration ranges of Cd²⁺. The IC₅₀ values of Cd²⁺ on in vitro ChE activity in brain and muscle tissues were 1.56 and 4.31 mM, respectively. Exposure of fish to environmentally relevant concentrations of Cd²⁺ (5–30 μg l^−l) for 28 days evoked only a transient inhibition (21–34%) of in vivo ChE activities. Prior exposure and co-exposure of fish to 15 μg l⁻¹ of Cd²⁺ enhanced the extent of inhibition of ChE levels induced by the organophosphorous insecticide chlorpyrifos. As high concentrations of cadmium have the potential to depress ChE activities, monitoring of metal levels in water bodies with suspected high levels of metal inputs is necessary to accurately interpret the fish ChE inhibition data in relation to insecticide contaminations.     

Effect of Interaction of Heavy Metals on (Na+-K+) ATPase and the Uptake of 3H-DA and 3H-NA in Rat Brain Synaptosomes

Abstract: The effect of interaction of Mn²⁺, Pb²⁺ and Cd²⁺ on (Na⁺-K⁺) ATPase and uptake of labelled dopamine (³H-DA) and labelled noradrenaline (³H-NA) were studied in vitro in rat brain synaptosomes. The inhibition of (Na⁺-K⁺) ATPase by Pb²⁺ and Cd²⁺ alone was concentration dependent, however, Mn²⁺ had almost no effect on the activity of this enzyme. Interaction of Cd²⁺ with either Pb²⁺ or Mn²⁺ was most powerful in inhibiting the activity of synaptosomal transport ATPase. Lower concentrations of Pb²⁺ increased while higher concentrations inhibited synaptosomal uptake of ³H-DA and ³H-NA. Lower concentrations of Cd²⁺ increased the uptake of ³H-DA while at concentrations of 100 μM, the uptake was inhibited, this metal had strong inhibitory effect on the uptake of ³H-NA. Mn²⁺ had inhibited the uptake of labelled amines. Interaction of Mn²⁺ with Pb²⁺ or Cd²⁺ produced inhibition on the uptake of ³H-DA and ³H-NA. The results of the uptake of biogenic amines in the presence of metal ions apparently had no correlation with the activity of (Na⁺-K⁺) ATPase which is involved in the active transport of cations across cell membranes.     

Movement of cadmium in rat submaxillary slices

The movement of ¹⁰⁹Cd²⁺ (as CdCl₂) was studied in rat submaxillary slices. Standard conditions included 10^?6m Cd²⁺, modified Krebs-Ringer-Tris phosphate buffer (pH 7.4), 37°C, and 100% O₂. A steady-state distribution was not reached within 180 min. Tissue uptake was proportional to the metal concentration in the medium, was decreased by lowering the temperature, and was not influenced by inhibition of oxidative (with N₂, 2,4-DNP, or NaCN) or glycolytic (with NaF) energy production. Uptake was decreased by incubation with Na₂EDTA but not by incubation with Na₂NTA. Zn²⁺, Cu²⁺, Fe²⁺, or Fe³⁺ did not alter the tissue uptake of Cd²⁺. A passive uptake was suggested. The rate of efflux and displacement of bound metal indicated firm, intracellular binding.     

Simultaneous recording of his bundle electrogram,electrocardiogram, and systolic tension from intact modified Langendorff rat heart preparations II. Dose-Response relationship of cadmium

A dose-response study was undertaken to evaluate further the suspected specificity shown by cadmium for the atrioventricular (A-V) nodal region of the myocardial conduction system. Using the previously developed method for recording electromechanical events of isolated hearts, the effects of 3 × 10^?2, 3 × 10^?3, and 3 × 10^?5 mm Cd²⁺ were studied. His bundle electrogram (HBE), ECG, and systolic tension analyses demonstrated a direct doseresponse relationship with increasing cadmium concentrations. Significant PR and A-H interval prolongations were evident at all concentrations of cadmium studied. Although depressed by greater cadmium concentrations, neither the H-V interval, the spontaneous heart rate, nor the systolic tensions were significantly affected by 3 × 10^?5 mm Cd²⁺ perfusion. These observations indicate that cadmium is a specific depressant of conduction in the region of the A-V node. Since cadmium is known to interfere with calcium-activated processes, it is proposed that cadmium may act by displacing membrane calcium and/or by altering cellular uptake of calcium. If cadmium does act to displace calcium in heart tissue, these results may also infer that cells of the A-V nodal region are selectively sensitive to cadmium because of a greater dependence on external calcium for the maintenance of cell excitability. The preferential selectivity shown by cadmium for specific cells in the cardiac conduction system is a unique finding which suggests that conduction tissue excitability may be partially dependent on external calcium uptake and distribution and/or the interactions of various trace and heavy metal ions.     

The influence of some complexing agents (EDTA and citrate) on the uptake of cadmium in perfused rainbow trout gills

The cadmium transfer through and the retention of metal in perfused gills from rainbow trout (Salmo gairdneri) has been studied in the presence of two Cd-complexing agents, ethylenediaminetetraacetic acid (EDTA) and citrate.The transfer and retention of Cd in the presence of EDTA was almost a function of the ambient free Cd²⁺ activity. The transfer of the free Cd ion was about 1000 times higher than of the Cd-EDTA complex. The Cd-EDTA complex was to some extent retained in perfused tissue.The transfer of Cd in the presence of citrate was markedly greater than expected on the basis of the free Cd²⁺ activity. The tissue retention of Cd was not affected by the presence of citrate.It is concluded that Cd uptake in fish gills in the presence of complexing agents is not simply a function of complexed versus free metal. The uptake is also profoundly dependent on the type of complexing agent present.     

Effect of cadmium on the extracellular Na+, K+, and Ca2+ in the gill and small intestine of Goldfish Carassius auratus

In this study, the toxic effect of cadmium on extracellular Na⁺, K⁺, and Ca²⁺ in the gill and small intestine of goldfish Carassius auratus was determined with the technique of ion chromatograph. Two-way ANOVA indicated that the two factors (Cd²⁺ treatment and time) and the interaction factor had significant effect on the level of Na⁺, K⁺, and Ca²⁺ in the small intestine and gill. 1.0 mg/L Cd²⁺ significantly increased Ca²⁺ level in the small intestine, but Ca²⁺ level in the gill was significantly decreased by 1.0 and 5.0 mg/L Cd²⁺ at 24, 48, and 72 h. Na⁺ and K⁺ level in the small intestine and gill was increased by 1.0 mg/L Cd²⁺ at three time points, but increased by 5.0 mg/L Cd²⁺ at a certain different time. In addition, Na⁺ level was significantly decreased by 5.0 mg/L Cd²⁺ at 24 or 48 h in the small intestine and gill. The results indicated that Cd²⁺ played an important role in regulating the level of Na⁺, K⁺, and Ca²⁺ in the small intestine and gill of goldfish C. auratus. A method was constructed to investigate the extracellular Na⁺, K⁺ and Ca²⁺ in the tissues of gold fish with ion chromatography.     

Effect of thiuram sulphides on the uptake and distribution of nickel in pregnant and non-pregnant mice

Oral administration of 63Ni2+ together with thiuram sulphides (tetramethylthiuram disulphide, tetraethylthiuram disulphide, tetrabutylthiuram disulphide, dipentamethylenethiuram monosulphide or dipentamethylenethiuram tetrasulphide) or sodium diethyldithiocarbamate resulted in highly increased levels of 63Ni2+ in several tissues of mice in comparison with animals given 63Ni2+ alone. Administration of these substances to pregnant animals induced increased levels of 63Ni2+ in the fetuses. The uptake of 63Ni2+ in the brains of both adults and fetuses was usually very markedly enhanced by these compounds--dipentamethylenethiuram monosulphide and tetraethylthiuram disulphide being the most efficient compounds in this respect. Determination of the chloroform/water partition coefficients for nickel in the presence of thiuram sulphides or sodium diethyldithiocarbamate showed that these compounds are able to form lipophilic complexes with the metal. A facilitated penetration through the cellular membranes of the lipophilic complexes between nickel and these substances can explain the effects on the fate of the nickel. However, the partition coefficient for nickel in presence of sodium diethyldithiocarbamate was much higher than for the thiuram sulphides, but in spite of that, the effect of sodium diethyldithiocarbamate on the disposition of 63Ni2+ in the mice was not more marked than for most of the thiuram sulphides. It has been shown that tetraethylthiuram disulphide undergoes a reductive fission in the gut to diethyldithiocarbamate, which is considered to be the active form of tetraethylthiuram disulphide. The marked effects on the disposition of the 63Ni2+ induced by the other thiuram sulphides examined in the present study suggest that a similar fission to chelating thiocarbamates will take place. However, the formation of lipophilic complexes with the original thiuram sulphides may contribute to the effects on the disposition of the 63Ni2+.     

Metals (Ag+, Cd2+, Cr6+) affect ATPase activity in the gill,kidney, and muscle of freshwater fish Oreochromis niloticus following acute and chronic exposures

Freshwater fish Oreochromis niloticus were individually acutely exposed to different concentrations (0, 0.1, 0.5, 1.0, and 1.5 μg/mL) of Cd²⁺, Cr⁶⁺, and Ag⁺ for 96 h and 0.05 μg/mL concentration of the same metals for different periods (0, 5, 10, 20, and 30 days) chronically. Following each experimental protocol, Na⁺/K⁺‐ATPase, Mg²⁺‐ATPase, and Ca²⁺‐ATPase activities were measured in the gill, kidney, and muscle of O. niloticus. In vitro experiments were also performed to determine the direct effects of metal ions (0, 0.1, 0.5, 1.0, and 1.5 μg/mL) on ATPases. Except Ag⁺, none of the metals caused fish mortality within 30 days. Silver killed all the fishes within 16 days. Metal exposures generally decreased Na⁺/K⁺‐ATPase and Ca²⁺‐ATPase activities in the tissues of O. niloticus, although there were some fluctuations in Mg²⁺‐ATPase activity. Ag⁺ and Cd²⁺ were found to be more toxic to ATPase activities than Cr⁶⁺. It was also observed that metal efficiency was higher in the gill than in the other tissues. Results indicated that the response of ATPases varied depending on metals, exposure types, and tissues. Because ATPases are sensitive to metal toxicity, their activity can give valuable data about fish physiology. Therefore, they may be used as a sensitive biomarker in environmental monitoring in contaminated waters. © 2011 Wiley Periodicals, Inc. Environ Toxicol 28: 707–717, 2013.     

The synthesis of metallothionein and cellular adaptation to metal toxicity in primary rat kidney epithelial cell cultures

Single cells were isolated from rat (100–150 g) kidney cortex slices by mild trypsinization. They were plated on plastic culture dishes and were maintained in a selective Eagle's D-Valine Minimum Essential Media (MEM) to form an epithelial cell monolayer culture. The fibroblast growth was retarded by D-Valine. The cells in monolayer culture accumulated cadmium when they were incubated with a ¹⁰⁹CdCl₂ (10^?5 M) containing medium. The synthesis of metallothionein by these cells was demonstrated by incorporation of [³⁵S]cysteine and ¹⁰⁹CdCl₂ into a heat stable protein (mol. wt 10 000) within 8 h of exposure and also by immunoprecipitation using a specific antibody to rat liver metallothionein. The cytotoxic effects of Zn²⁺, Cu²⁺, Cd²⁺ and Hg²⁺ were studied in culture after addition of various concentrations of metal salts (10^?5 –10^?2 M). Disrupted cellular colonies with severe cell damage were observed after addition of 10^?3 M Cd²⁺ or Hg²⁺ as CdCl₂ or HgCl₂ while similar toxicity was observed only after addition of 10^?2 M Zn²⁺ or Cu²⁺ as ZnSO₄ or CuSO₄ to confluent cell cultures. The cellular damage due to Cd²⁺ was protected when the cells were pretreated with Cd²⁺ (10^?5 M) for 24 h and these cells could tolerate much higher concentrations of cadmium (10^?2 M). These results indicate a direct protective role of intracellular metallothionein in the cellular toxicity of cadmium.     

The Binding of Cadmium Ions to the Smooth Muscle of Guinea-Pig Taenia Coli

Abstract: Taenia coli was used to study the property of binding of Cd²⁺. The Scatchard plots of cadmium uptake showed that two qualitative Cd²⁺ binding sites (high and low affinity binding sites) exist in taenia coli. Decrease in Ca²⁺ concentration in the medium did increase the cadmium binding. The Scatchard analysis of Cd²⁺ binding in taenia coli at 4° indicated a single class of binding sites (only high affinity binding sites). These findings suggest that the greater number of high affinity Cd²⁺ binding sites in taenia coli may relate to the binding to cell membrane. Further, it was postulated that some of low affinity binding sites in taenia coli may reflect intracellular accumulation, indicating the action on the contractile system.     

Comparison of some biochemical effects of teratogenic doses of mercuric mercury and cadmium in the pregnant rat

Mercuric mercury (Hg²⁺), like cadmium (Cd²⁺), interferes with the transport of certain essential metals to the conceptus in the pregnant Wistar rat and, at 48 h after the IV injection of a teratogenic dose (0.79 mg Hg²⁺/kg body weight) on day 12 of gestation, the foetal concentrations of Zn²⁺, Cu²⁺ and Fe³⁺, but not of Mg²⁺, are reduced significantly. Both Hg²⁺ and Cd²⁺, at teratogenic dose levels, inhibit the placental and foetal uptake of ⁶⁵Zn²⁺ and ⁶⁷Cu²⁺, but possibly by different mechanisms. In addition, the effects of Hg²⁺, at different times after dosing, on the uptake of these labelled tracers and of ⁵⁹Fe³⁺, administered as 15-min pulses, do not parallel the changes in the placental and foetal concentrations and contents of the endogenous, stable metallic ions. The teratogenic dose of Hg²⁺ inhibits the placental and foetal uptake of L-[4,5-³H]-leucine, but not the incorporation of the labelled amino acid into foetal protein. In contrast, the corresponding dose of Cd²⁺ inhibits both leucine uptake and protein synthesis in the placenta and foetus. Similarly, Cd²⁺ inhibits the uptake of [2-¹⁴C]-thymidine and its incorporation into foetal DNA, whereas Hg²⁺ reduces the placental and foetal uptake, but has little or no effect on the utilization of the nucleoside. Since both Cd²⁺ and Hg²⁺ reduce the foetal uptake of ⁶⁵Zn and the foetal concentration of Zn, but only Cd²⁺ interferes with DNA synthesis, it is unlikely that the inhibition of the metabolism of thymidine can be attributed to reduction in thymidine kinase activity in consequence of foetal Zn deficiency. It is concluded that the small amount of Cd²⁺ that is taken up by the foetus has a direct effect on the synthesis of DNA and protein, whereas Hg²⁺ primarily affects placental transport processes.     

Effect of cadmium on epithelial membranes

Cd²⁺ (10^?3m) on the external side of the frog skin, increased the electrical potential difference (PD), short-circuit current (SCC), and resistance across this membrane. The effect was irreversible. Cd²⁺ (10^?3m) on the serosal side of the toad urinary bladder inhibited the SCC, but this was increased by 10^?3m and 10^?4m at the mucosa or 10^?4m at the serosa. The increases in SCC were inhibited by amiloride, indicating the effect was due to a stimulation of active transmural sodium transport. The increased resistance seen in the frog skin may reflect a decreased permeability to chloride. These results indicate that cadmium can influence active ion transport and the permeability of epithelial membranes.