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Showing papers on "Lead acetate published in 1974"


Journal ArticleDOI
TL;DR: An animal model of lead poisoning was developed in which suckling mice were exposed to lead acetate from birth indirectly through their mothers and then directly after weaning, and lead-treated hyperactive mice responded paradoxically to all drugs except chloral hydrate.

159 citations


Journal ArticleDOI
TL;DR: Lead increased the response of the mice to all classes of viruses against which it was tested and represses the anti-EMCV protective effects of both PIC and of NDV, which, in other reports, were shown to induce IF in radioresistant macrophages or in radiosensitive lymphocytes.
Abstract: Lead acetate was administered continuously in the drinking water to CD–1 male mice beginning at 4 weeks of age. An LD10–20 of the lytic viruses or 300 plaque-forming units of RLV was inoculated int...

75 citations



Journal ArticleDOI
TL;DR: The present procedure is proposed as a model for studies of the subtle effects of lead on the central nervous system and it is found that a lactating mother rat consuming 5% lead acetate in the diet produced milk containing 25 ppm lead.

66 citations


Journal ArticleDOI
TL;DR: The data suggest that the infant nonhuman primate is much more susceptible to lead intoxication than is the adult, and their use as an experimental model to evaluate lead intoxication is suggested.
Abstract: When infant rhesus monkeys were exposed to lead via the addition of lead acetate (0.5–9 mg/kg body weight) to their formula or by the consumption of lead particles from lead-based surrogate mothers...

63 citations


Journal ArticleDOI
TL;DR: It is suggested that lead produces an animal model ofhyperactivity which may have clinical relevance and which may explain some cases of hyperactivity in children.
Abstract: Mice were exposed to lead from birth by substituting solutions of lead acetate for the drinking water of their mothers. The suckling mice were thus exposed to lead through their mother's milk and, at weaning, directly through the drinking water. Controls received equal concentrations of sodium acetate. No deaths of offspring or mothers occurred during the first 90 days of exposure. It has been suggested recently that lead exposure may account for some incidences of behavior disorders in children. Levels of motor activity of individual offspring were measured from weaning until 70 days of age in specially designed activity cages. Lead-treated mice were more than three times as active as age-matched or size-matched controls. Treated and control animals were administered drugs currently used in the treatment and diagnosis of hyperactivity in children. All control animals responded as expected to all drugs used in this study. However, lead-treated mice responded paradoxically to d- and l-amphetamine, methylphenidate, and phenobarbital. That is, the CNS stimulants suppressed their hyperactivity while phenobarbital exacerbated the lead-induced hyperactivity. These findings suggest that lead produces an animal model of hyperactivity which may have clinical relevance and which may explain some cases of hyperactivity in children.

62 citations


Journal ArticleDOI
TL;DR: This composite study suggests that hepatic parenchymal cell dysfunction is one facet of the pathophysiology manifested by cadmium or lead interaction with endotoxin, and indicates that endotoxin sensitivity induced by lead or Cadmium cannot be attributed to phagocytic alterations.

60 citations


Journal ArticleDOI
TL;DR: The presence of food in the gastrointestinal tract reduced lead absorption when a tracer dose was administered but did not affect absorption after 2 mg of Pb/kg po, and the chelators nitrilotriacetic acid and sodium citrate increased absorption of lead, as did orange juice, a source of citric acid.

53 citations


Journal ArticleDOI
TL;DR: A large number of studies have shown that exposure to inorganic lead produces cerebral dysfunction and clinically definable encephalopathies in man, but few studies have studied the biochemical changes in brain following exposure to the substance.
Abstract: Inorganic lead produces cerebral dysfunction and clinically definable encephalopathies in man. To date there have been few studies on the biochemical changes in brain following exposure to inorganic lead. Studies correlating toxicity with behavioral and brain neurochemical changes following lead exposure have been hindered because adult laboratory animals are resistant to the central nervous system effects of lead poisoning. Such studies have been impeded by lack of suitable experimental models until Pentschew and Garro showed that brain lesions develop in neonatal rats when a pregnant rat newly delivered of her litter is placed on a 4% lead carbonate containing diet. Lead passes into the developing sucklings via maternal milk. Lead-poisoned new-borns have pronounced retardation of growth and during the fourth week of ilfe develop the severe signs of lead encephalopathy, namely, extensive histological lesions of the cerebellum, brain edema, and paraplegia. There is an approximate 85-fold increase in the lead concentration of both the cerebellum and cerebral cortex relative to controls, but edema and gross vascular changes are confined to the cerebellum. Ingested lead had little effect on RNA, DNA, and protein concentrations of developing rat cerebellum and cerebral cortex. However, there was a reduction of between 10 and 20% in the DNA content of the cerebellum around 3 weeks of age in the lead-exposed sucklings. This suggests a failure of cell multiplication in this part of the brain.A critical evaluation of this experimental approach indicated that under similar dietary conditions experimental lactating rats eat 30% less food than controls resulting in: (a) sustained loss in body weight of nursing mothers and that (b) offsprings who develop paraplegia and cerebellar damage do so after gaining access to lead containing diet. We have studied mothers' food consumption and body weight changes and blood, milk, and brain lead content; and newborns' body and brain weight changes, blood and brain lead content, and brain serotonin (5HT), norepinephrine (NE), dopamine (DA), and gamma-aminobutyric acid (GABA). We have found that a lactating mother rat eating 5% lead acetate (2.73% Pb) produced milk containing 25 ppm lead. When the mothers' diet is changed at day 16 from 5% PbAc to one containing 25 ppm Pb, and neonates allowed free access to the solid diet, the sucklings still have retarded body growth but do not develop paraplegia or grossly apparent vascular damage of the cerebellum. However, during the fourth week these animals exhibit a less severe form of "encephalopathy" consisting of hyperactivity, tremors, and stereotype behavior. Pair-fed controls coetaneous to experimental groups do not display such activities. There was no change in brain 5HT, GABA, or NE, but a 15-20% decrease in brain DA. Change in DA relative to other monoamines suggests a relationship between CNS dysfunction due to lead and DA metabolism in the brain.The experimental design as discribed provides a model of CNS dysfunction due to lead exposure without debilitating histopathologies. It is possible that our findings on increased motor activity and changes in brain dopamine may correspond to early responses to lead exposure before recognized overt signs of toxicity.

50 citations


Journal Article
TL;DR: It is apparent from these findings that chickens are more resistant to lead poisoning than humans, horses, dogs and wild fowl such as ducks.
Abstract: The effect of aqueous lead acetate given per os to chickens for 35 consecutive days and the effect of lead on interferon and antibody production was investigated. Chickens were found to tolerate levels of lead as high as 160 mg/kg/day without exhibiting clinical signs or hematological changes in spite of very high levels of lead in the blood (6.2 ppm). It is apparent from these findings that chickens are more resistant to lead poisoning than humans, horses, dogs and wild fowl such as ducks. Subclinical lead doses did not affect interferon induction in response to statolon and Newcastle Disease virus (NDV)-B(1). Interferon concentrations and duration in serum were markedly decreased in chickens which received lead at the 320 mg/kg level. Long time lead exposure had no marked effect on antibody production to NDV in chickens. No consistent correlation was observed between blood lead concentration and antibody titer. The results of these studies indicate that long term subclinical lead intake suppresses neither interferon nor antibody production in chickens.

43 citations


Journal ArticleDOI
TL;DR: A significant retardation was observed in both brain parts of rats suckling from mothers ingesting lead and the labelling of glutamine was particularly low in comparison with glutamate, aspartate and γ‐aminobutyrate.
Abstract: —The development with age of the pattern of distribution of glucose carbon characteristic of the adult brain was studied in 7-, 13-, 19- and 24-day-old rats suckling from mothers maintained on a diet containing 4·5% lead acetate or on a normal diet. In normal rats the rapid and extensive conversion of glucose carbon into amino acids associated with the tricarboxylic acid cycle has been shown to develop in the cerebellum and the cerebral cortex during the same period as previously observed for the whole forebrain. A significant retardation was observed in both brain parts of rats suckling from mothers ingesting lead. In comparison with glutamate, aspartate and γ-aminobutyrate, the labelling of glutamine was particularly low. The concentration of glutamine was not affected in the forebrain, but it was elevated in the cerebellum. The age-dependent rise in the amounts of glutamate and aspartate was also retarded, but it would appear that the contribution of this effect to the depressed labelling of amino acids was small. There was no evidence of impaired entry of glucose into the brain from the blood. Although in comparison with undernourished animals, the growth retardation of the lead-treated rats is similar, several of the effects observed on the developing brain seem to be distinct.

Journal ArticleDOI
TL;DR: The results indicate a lower toxicity of lead acetate in young animals than in adults and a higher toxicity ofLead in adult males and both groups of young animals.
Abstract: The toxicity of lead acetate was determined in young (3-week-old) and adult (18-week-old) rats of both sexes 8 days after a single i.p. injection. The LD50 was lower in adult males than in adult females and both groups of young animals.

Journal ArticleDOI
11 Jan 1974-Science
TL;DR: Weanling rats eating a low calcium diet voluntarily ingested lead acetate solutions in much greater proportions than did iron-deficient or control weanlings, indicating an absence of behavioral regulation of body lead levels.
Abstract: Weanling rats eating a low calcium diet voluntarily ingested lead acetate solutions in much greater proportions than did iron-deficient or control weanlings. This increased ingestion occurred even with high concentrations of lead acetate which normal weanlings found extremely aversive. Chronic injections of lead acetate into weanlings did not change lead ingestion, indicating an absence of behavioral regulation of body lead levels. Female lead-injected weanlings did show a significant increase in calcium ingestion. Calcium deficiency may be one component of lead pica.

Journal ArticleDOI
TL;DR: It is shown that lead may be bound within the cell wall, and that it may also enter the cytoplasm, in the leaf cells of mosses exposed to environmental pollution.
Abstract: An electron microscope study of experimental and environmental lead poisoning of leaf cells from the moss Rhytidiadelphus squarrosus (Hedw.) Warnst. is described. Plants treated with lead acetate and lead chloride solutions, or collected from roadsides exposed to lead pollution from motor exhaust gases have been used. The results are compared with other studies of experimental lead poisoning in both plants and animals, with particular regard to uptake mechanisms and to lead accumulating at different sites in the cell. We have shown that lead may be bound within the cell wall, and that it may also enter the cytoplasm. Pinocytosis was observed in leaf cells from moss plants treated with lead salt solutions. Via pinocytotic vesicles within the cytoplasm the particles containing lead could then be discharged into the vacuole. In the leaf cells of mosses exposed to environmental pollution the protoplasmic lead was found to be bound within the nucleus, and was easily identified as electron-dense, nuclea...

Journal ArticleDOI
TL;DR: Changes in the rate of conversion of both precursors into amino acids associated with the tricarboxylic acid cycle were observed in rats suckling from mothers fed either a normal diet or a diet containing 4·5% lead acetate.
Abstract: —[2-14C]Glucose and [3H]acetate were injected simultaneously into 19-day-old rats suckling from mothers fed either a normal diet or a diet containing 4·5% lead acetate. Changes in the rate of conversion of both precursors into amino acids associated with the tricarboxylic acid cycle were observed. [I4C]Glucose. In the brain of young rats ingesting lead, the specific radioactivity of glutamate, aspartate, γ-aminobutyrate and glutamine were all significantly lowered relative to that of glucose. Glutamine labelling was the most affected. [3H]Acetate. In comparison with controls, the total amount of 3H in either water or acid-soluble constituents of the brain was the same, but the 3H content of the amino acids was significantly reduced in the lead-treated rats. In both groups, glutamine had the highest specific radioactivity but the time courses of the labelling of glutamine were different. In the control the peak incorporation was reached during the first 5 min, whereas in the experimental animals this occurred at about 10 min after the injection of the precursor, and the specific radioactivity even at that time was less than in controls. When compared with controls, the depression in the labelling of glutamine was accompanied at 5 min by an increase in the specific radioactivity of aspartate. In the lead-treated rats the labelling of GABA was also slowed and the time course seemed to follow that of glutamine rather than glutamate. In spite of the differences in the metabolism of [3H]acetate, metabolic compartmentation of glutamate, assessed by a glutamine : glutamate specific radioactivity ratio higher than 1, was evident even in the brain of the lead-treated animals, although the values of the ratio at 5 and 10 min were less than in controls. There was no evidence of a diminished supply of substrates to the brain in lead intoxication. The overall changes would be consistent with a retardation in the biochemical maturation of the brain in terms of development of glucose metabolism and metabolic compartmentation.

Journal ArticleDOI
TL;DR: Doses of lead acetate greater than 20 $mu$g per day decreased the transfer of both calcium and strontium across the duodenal wall and these transfers decreased further with increased doses of lead, an effect which was independent of whether the rats were killed on the 8th or 15th day of the experiment.

Journal ArticleDOI
TL;DR: The quantitative changes of the endoplasmic reticulum and in the number of free ribosomes (polysomes) as well as the fingerprint-like membrane whorls indicate an interference of lead with protein synthesis.
Abstract: Introduction Even small quantities of lead inhibit the respiratory chain and the hemoglobin synthesis as well as the gluconeogenesis. Lead is concentrated in mitochondria and lysosomes. Therefore, it was of interest to analyse morphometrically the adaptability of liver parenchymal cells of juvenile rats to lead overload. Material and Methods 20 10-day-old male Wistar rats were used — During 2 weeks, 15 of these animals were injected i. p. 0,2 ml of a 1% lead acetate solution. Afterwards they were seperated from their mothers and given free access to food and tap water. During 2 additional weeks lead acetate was added to the tap water. 5 untreated rats served as controls. After 4 weeks the animals were sacrified. Morphometric analysis was made according to Weibel et al., 1969. Results After 4 weeks of lead overload, nuclear invaginations and intranuclear lipid inclusions occur. Giant lysosomes contain osmiophilic granular material and damaged mitochondria. Fingerprint-like mebrane whorls can be observed. The number of mitochondria per unit volume of cytoplasm decreases without changes in mean volume of mitochondria. The total surface of cristae per unit cytoplasmic volume increases by 20%. The RER increases its mebranes and volume by 50%. The volume of the free ribosomes increases, too. SER and lysosomes lose part of their volume. Discussion Under the influence of a 4 week lead overload a change in nuclear morphology occurs. The number of mitochondria decreases probably due to blocked chondriogenesis. The proliferation of cristae membranes is considered a consequence of a disintegrated membran formation. The quantitative changes of the endoplasmic reticulum and in the number of free ribosomes (polysomes) as well as the fingerprint-like membrane whorls indicate an interference of lead with protein synthesis.

Journal Article
TL;DR: A hypothesis has been formulated that relates the more efficient nephron of the gerbil kidney to the rapid and extensive development of intranuclear inclusion bodies and the greater accumulation of total lead.
Abstract: Mongolian gerbils fed diets containing lead acetate maintained body weight comparable to gerbils fed the same diet without added lead. Intranuclear lead inclusion bodies in epithelial cells of the proximal convoluted tubules of the kidney were first observed at 4 weeks, and increased in number to about 50 per high power field at 12 weeks. At this time, a corticomedullary area of empty-appearing tubules was prominent. Transmission electron microscopy confirmed the increase in number and size of nuclear lead inclusion over the 12-week period. Cytoplasmic changes observed in proximal tubule cells containing lead inclusions were considered indicative of acute lethal injury. Distinct cytoplasmic fibrillar structures, first apparent at 8 weeks, were present in some proximal tubular lining cells and strongly resembled newly formed intranuclear lead inclusions. After 12 weeks, the total amount of lead present in the gerbil kidney was four to six times greater than that in rat kidney as determined by atomic absorption spectrophotometry. A hypothesis has been formulated that relates the more efficient nephron of the gerbil kidney to the rapid and extensive development of intranuclear inclusion bodies and the greater accumulation of total lead.

Journal ArticleDOI
TL;DR: The data on hepatic gluconeogenesis support a mitochondrial locus of lead action and suggest that defects in hepatatic glucoregulation may play a role in the toxicity of acute lead poisoning.
Abstract: SummaryMale rats were administered either 5 mg lead acetate or sodium acetate iv and then fasted overnight. Gluconeogenesis was assessed both in vivo employing radiotracer as well as chemical conversions of alanine to glucose, and in vitro using isolated hepatocytes. Lead-treated rats had depressions in both 14C-alanine incorporation into blood glucose and the hyperglycemic response to an alanine load. Isolated hepatocyte gluconeogenesis from either 10 mM alanine, lactate or pyruvate was depressed from 40 to 60% for lead-treated rats as compared to controls; the addition of lead acetate to normal hepatocytes in vitro had no effect on gluconeogenesis. Glucose synthesis from three precursors which do not require a mitochondrial step for conversion to glucose—i.e., fructose, glycerol, and oxaloacetate—was not markedly depressed in hepatocytes from lead-treated rats. Incorporation of 14C-alanine into both glucose and carbon dioxide were also depressed following lead treatment. These data on hepatic gluconeoge...

Journal ArticleDOI
TL;DR: CAMP-PD and 5 nucleotidase was demonstrated histochemically in the cervicovaginal epithelium of 3-day-old mice and enhanced in mice treated with estradiol and the authors considered these enzymes active in estrogens mechanism of action.
Abstract: Cyclic-35-adenosine monophosphate phosphodiesterase (cAMP-PD) and 5-nucleotidase were demonstrated histochemically in the cervicovaginal epithelium of 3-day-old mice and enhanced in mice treated with estradiol. The incubation medium for cAMP-PD was .05 M tris-maleate buffer pH 7.6-7.7 with .01 M MgC12 2 mM lead acetate .1-1 mg per ml snake venom (source of 5-nucleotidase) 1.53 mM cAMP and .1 M theophylline. The 5nucleotidase medium was .2 M tris-maleate buffer pH 7.2 .1 M MgS04 1.8 mM lead nitrate 3.8 mM 5AMP. In 3-day-old control mice cAMP-PD was seen in the apical or luminal plasma membrane of the epithelial cells. 5 mcg estradiol-17beta daily for 2 days broadened the lead deposit; 5 injections of estradiol further increased cAMP-PD activity. Theophylline decreased the activity. Almost no 5 nucleotidase was present in newborns and in 3-day-old mice but nucleotidase was increased by estradiol in the superficial part of the epithelial cells. The authors considered these enzymes active in estrogens mechanism of action.


01 Jan 1974
TL;DR: The energy dependent biosyntheses of protein and phospholipid were unaffected by lead and cadmium treatment suggesting that energy metabolism and oxidative phosphorylation were not affected appreciably.
Abstract: The biochemistry of leukocytes derived from peripheral blood of rabbits treated with lead or cadmium salts was examined. Rabbits were injected daily for 7 or 21 days with saline, 10 mg/kg lead acetate, or 1 mg/kg cadmium chloride. Leukocytes were isolated from the rabbits blood. Aliquots of cells were incubated with 3H-thymidine, 14C-uridine, 3H-leucine, and 14C-choline. The lead and cadmium treatments only marginally influenced the blood values. The outstanding metabolic result was a 6.5 and 3.3 fold depression of 3H-thymidine incorporation in the one and three week cadmium treated animals, respectively. The 14C-uridine incorporation was depressed 1.7 and 2.5 fold at the same time. Lead and cadmium treatments did not affect the incorporation of 3H-leucine and 14C-choline or the depletion rate of leucine. Choline depletion was accelerated slightly after three weeks of treatment with either metal. The energy dependent biosyntheses of protein and phospholipid were unaffected by lead and cadmium treatment suggesting that energy metabolism and oxidative phosphorylation were not affected appreciably. The depressive effect of these metals on DNA synthesis may result from a direct interaction with DNA causing a disruption of the replicative process. Leukocytes are a responsive bio-indicator of lead and cadmium intoxication.