Showing papers on "Lead acetate published in 1990"

Indirect mechanism of lead-induced genotoxicity in cultured mammalian cells

Abstract: The data concerning the mutagenic, clastogenic and carcinogenic properties of inorganic lead compounds have been conflicting. To investigate whether the genotoxicity of lead is due to indirect effects such as interference with DNA-repair processes, the induction of mutations, sister-chromatid exchanges and strand breaks by lead ions alone as well as in combination with UV light as a standard mutagen were determined. Lead acetate alone does not induce DNA-strand breaks in HeLa cells or mutations at the HPRT locus and sister-chromatid exchanges in V79 Chinese hamster cells. However, at all endpoints tested, lead ions interfere with the processing of UV-induced DNA damage. They inhibit the closing of DNA-strand breaks after UV irradiation and enhance the number of UV-induced mutations and sister-chromatid exchanges, indicating an inhibition of DNA repair. These data point out the necessity to consider such indirect effects when assessing the genotoxicity of metal compounds. As possible mechanisms of repair inhibition we suggest either the interaction with repair enzymes such as polymerase or ligase or else the interaction with calcium-regulated processes, for example with calmodulin.

The effect of duration of exposure on the expression of lead toxicity on the male reproductive axis.

Abstract: This study assesses the significance of duration of exposure on the expression of lead toxicity on the male reproductive system. Male Wistar rats, 52 days old, were treated with 0.0% or 0.6% lead acetate in their water for 7, 14, 30, or 60 days prior to sacrifice. In all cases, the lead-treated groups had blood lead and free erythrocyte protoporphyrin (FEP) levels significantly higher than control animals (P less than 0.0001). Serum testosterone levels and spermatogenesis were suppressed in all lead-treated groups compared to the corresponding controls (P less than 0.05 and P less than 0.001, respectively), except for the group treated for 7 days. The data presented verify that exposure to lead acetate is toxic to the reproductive axis in male rats, but that increased duration of exposure after 14 days does not further suppress serum testosterone levels or spermatogenesis.

Toxicity of lead acetate to female rabbits after chronic subcutaneous administration. 1. Biochemical and clinical effects

Abstract: The effect of chronic subcutaneous administration of lead acetate was studied in female rabbits. The low-dose group (15 animals) received three times a week 0.10–0.20 μg/kg body weight and the high-dose group (15 animals) 0.80–1.20 μg/kg. The control group received the vehicle only. Concentrations of lead in blood in the low-dose group increased to ca. 400 μg/l after 70 days and in the high-dose group to ca. 900 μg/l after 110 days. After 7.5 months eight animals of each group were sacrificed. The remaining rabbits were kept for an additional 4 months without treatment. Blood lead concentrations decreased with a half-time of 60–70 days. During exposure the gain in body weight was lower in the high-dose group than in the control group and the low-dose group. The high-dose group developed slight anaemia and low MCV, MCH and MCHC, and basophilic stippling of erythrocytes. These effects disappeared during recovery. ALAD activity in erythrocytes was very low during exposure in both exposed groups and did not reach control values during recovery. During exposure the concentrations of ZPP and ALA-U increased, but only ALA-U returned to normal during recovery. No other effects of lead on the composition of the urine were observed. No effects were observed on plasma urea and creatinine concentrations. In the highdose group the concentration of ALAD in the liver decreased by 30%. During recovery this effect was no longer present. No effects were seen in cytochrome P-450 content or cytochrome P-450-dependent enzyme activities. Lead was mainly stored in bones, but some also in serveral soft tissues. After recovery the concentrations in soft tissues decreased to a variable degree. In the high-dose group the relative weights of heart and liver increased. These effects disappeared during recovery. At 400 μg lead/l blood no adverse effects were observed that did occur at the high dose level.

Influence of chronic lead exposure on hormone levels in developing rats.

Abstract: The effect of five months' exposure to 0.5% lead acetate in drinking water on hormone levels of developing rats was studied. The hypothalamic and striatic concentrations of noradrenaline (NA) were decreased in both sexes. In female but not in male rats, blood and adrenal catecholamines and serum corticosterone concentrations were aiso increased. No changes were observed in serum thyroxine and 3,5,3′-triiodothyronine levels. Our results indicate that female developing rats are more susceptible to lead than male rats. In female rats, both the hypothalamo-pituitary-adrenal and sympatho-adrenal systems seem to be affected by this lead exposure; in male rats, only the latter system is affected.

Effects of lead on neurophysiological and performance measures: animal and human data.

Abstract: This paper reports lead-induced changes in neuropsychological measures and behavioral performance measures in monkeys and children. Monkeys were pre- and postnatally exposed to lead via the diet. Blood lead levels at the time of testing were 9.3, 40.3, and 55.7 micrograms/dL in controls, and animals exposed to 350 ppm or 600 ppm lead acetate, respectively. Flash-evoked and brainstem auditory-evoked potentials were recorded in adult animals. Results indicate latency increases in both measures as well as amplitude decreases in the flash-evoked response. Delayed reaction time and serial choice reaction were determined as measures of behavioral performance in lead-exposed school-age children from two lead smelter areas. In addition, pattern-reversal-evoked potentials and nerve conduction velocity were investigated. Neither nerve conduction velocity nor latency of the pattern-reversal-evoked potential were consistently influenced by lead. Of the behavioral measures, serial choice reaction performance revealed a consistent lead-related deficit, which became more pronounced with increasing task difficulty.

Treatment of acute lead intoxication. A quantitative comparison of a number of chelating agents.

Abstract: The efficacy of several chelating agents in alleviating acute lead intoxication has been investigated in male Swiss mice. The relative effectiveness of diethyl-enetriaminepentaacetic acid (DTPA), ethyleneglycolbis-(β-amino-ethylether)-N,N′-tetraacetic acid (EGTA), cyclohexanediaminetetraacetic acid (CDTA), L-cysteine, N-acetyl-L-cysteine (NAC), ascorbic acid, sodium diethyldithiocarbamate (DDC), 2,3-dimercaptosuccinic acid (DMSA) and sodium 2,3-dimercapto-1-propanesulfonate (DMPS) in reducing lethality of lead was examined. Significant increases in survival were noted with CDTA, ascorbic acid, DMSA, and DMPS. Therapeutic effectiveness (TEF) was determined for these compounds; TEF for ethylenediamine-tetraacetic acid (EDTA) and for 2,3-dimercaptopropanol (BAL) was also determined; CDTA (2.33) and EDTA (1.73) showed the highest values. In subsequent experiments, the effect of the chelating agents on the distribution and excretion of lead was investigated. Lead acetate trihydrate was administered subcutaneously at doses of 37.8 mmol/kg (LD50), and fifteen minutes later, chelators were given intraperitoneally at doses approximately equal to one-fourth of their respective LD50 values. EDTA, DTPA and CDTA were the most effective agents in increasing the urinary excretion of lead, whereas DTPA, CDTA, and DDC increased significantly the fecal excretion of lead. EDTA, DDC, and CDTA were the most effective chelators in reducing the concentration of lead found in various tissues. On the basis of these results, CDTA may be considered as an alternative in the treatment of acute lead poisoning.

Regional alterations of brain biogenic amines and GABA/glutamate levels in rats following chronic lead exposure during neonatal development.

Abstract: Wistar rat pups were administered either a high dose of lead acetate (400 μg lead/g body weight/day) or a low dose (100 μg lead/g body weight/day) by gastric intubation, from 2 days through 60 days of age. The rats on both these doses exhibited statistically significant decreases in body and brain weights throughout the lead treatment period. A group of rats on high dose was also rehabilitated by discontinuing the lead from 60 days of age. In these rats, at 160 days of age, the body weight but not the brain weight recovered to normal levels. During the lead intake, the rats on high dose revealed significant elevations in the levels of noradrenaline (NA) in the hippocampus (HI), cerebellum (CE), hypothalamus (HY), brainstem (BS), and accumbens-striatum (SA). The elevated levels in all the above regions except in the HY persisted even after rehabilitation. The dopamine (DA) levels changed significantly in opposite directions in HY (elevation) and BS (reduction) during the lead treatment, and the HY recovered after rehabilitation. Under lead, the serotonin (5HT) levels were elevated significantly in the HI, BS and MC (motor cortex), while after rehabilitation the abnormality persisted only in the MC. Low dose lead treatment was also effective on the same areas of brain. In the low dose group, estimation of the levels of GABA and glutamate were also done, and a significant decrease of GABA in CE and glutamate in MC was observed. The differences observed in the neurotoxic effects (none or significant) of lead in the different regions for each of the transmitters (NA, DA, 5HT) supports the interesting conclusion that the vulnerability of the axon terminals of any given type is dependent on some regional factors, although the projections of the different regions originate from an apparently similar category of neurons in the brain stem.

Saturnism in the male rat: endocrine effects.

Abstract: The effect of exposure to lead on endocrine function was studied in pubertal rats treated with 1.0 g/l lead acetate (PbAc) in drinking water for 20 days (subacute group) or 9 months (chronic group) in addition to iv injections of PbAc (0.1 mg/100 g body weight) every 10 (subacute group) or 15 days (chronic group). Although basal levels of testosterone were higher both in the plasma and in the testes of acutely intoxicated animals, the circulating levels of luteinizing hormone (LH) were not affected in either group, nor was the LHRH content of the median eminence. The density of [125I]LH/hCG binding sites in testicular homogenates was reduced by saturnism in both groups. However, the apparent affinity constant of the hormone-receptor complex significantly increased. These data can be viewed as the result of a mixture of specific lead toxicity (e.g., at the enzyme level) with other more general actions (e.g., at the level of the hypothalamus-pituitary-testicular axis).

The effects of thiamin on the tissue distribution of lead.

Abstract: The effects of thiamin on the tissue distribution of lead were evaluated in Sprague-Dawley rats exposed to 1000 ppm lead acetate in drinking water and treated daily with thiamin (25 or 50 mg kg-1 body weight, i.p.), calcium ethylenediamine tetraacetic acid (50 mg kg-1 body weight, i.p.) or their combination for 8 weeks. The subtoxic dose of lead did not alter weight gains, feed and water consumption during the treatment period. Thiamin decreased the blood (P less than 0.0001), liver (P less than 0.0001) and kidney (P less than 0.0001) concentrations of lead. Thiamin (50 mg kg-1 body weight) reduced the lead concentrations in tissues more effectively than thiamin (25 mg kg-1 body weight). The combined treatment was more effective than the respective individual treatments.

Combined effects of methylmercury, lead, and cadmium on hepatic metallothionein and metal concentrations in the Pekin Duck

Abstract: This study was initiated to determine the effects of combined treatments of methylmercuric chloride (MeHg), lead acetate (Pb) and cadmium chloride (Cd) administered orally on metallothionein (MT) and metal levels in the liver of the pekin duck (Anas platyrynchos). Methylmercury and Pb induced a two-fold increase in MT while Cd caused a seven-fold increase over controls. Concurrent administration of MeHg and Pb caused no increase in MT over single treatments. The hepatic MT content of the MeHg + Cd and MeHg + Pb + Cd groups was not different from the Cdalone group. Hepatic lead levels were lowest followed by Hg and Cd. Lead increased Hg levels when given simultaneously with MeHg, and further addition of Cd increased this effect. In groups given Pb, MeHg increased hepatic levels of this element, but when MeHg was also given with Cd, the combination produced a reduction in levels of Pb. Lead or MeHg had no effect on Cd levels. Methylmercury, Pb, and their combination elevated hepatic Cu over controls. All treatments significantly raised hepatic Zn levels above controls. Combinations of Cd with either MeHg or Pb lowered Zn levels below that caused by Cd alone. The simultaneous administration of all three metals did not produce Zn levels which were additive. The liver content of iron was not significantly altered.

[Effects of lead on drug metabolizing enzymes, cytochrome P-450 and hemeoxygenase in rats].

Abstract: The effects of lead on the drug metabolizing system in liver microsomes and porphyrin metabolism in the bone marrow were studied using male Wistar rats (about 250 g in weight). To study the acute effects of lead, rats were given lead injection intraperitoneally once a day for three consecutive days at a dose of 0 (control), 0.1, 1.0, 10 or 50 mg/kg of lead in the form of lead acetate in a 5% glucose solution. In the 2nd experiment, the chronic effects of lead were studied by administering lead at a dose of 0 (control), 5 and 20 mg/kg once a week for 9 wk for a total of 10 administrations. After the last injection, each rat was fasted for 22 h in a metabolic cage to prevent the animal from eating bed chips or feces and was then sacrificed by decapitation. The rat liver microsome enzymes were used to evaluate the effects of lead on the hepatic functions. In the acute stage, lead decreased the activities of drug metabolizing enzymes, such as aniline hydroxylase and aminopyrine N-demethylase, and decreased the contents of microsomal cytochrome P-450 and cytochrome b5. In the chronic stage, lead decreased the cytochrome P-450 and cytochrome b5 contents and induced hypertrophic liver, but did not affect the activity of aniline hydroxylase. These findings suggest that the rat gradually gained resistance against lead toxicity in the chronic stage. In a supplementary experiment, lead was found to decrease the contents of heme in the microsome and to increase the activity of hemeoxygenase.(ABSTRACT TRUNCATED AT 250 WORDS)

Lack of lead effects on fetal development and offspring learning when combined with alcohol in the Long-Evans rat

Abstract: Two studies were conducted to evaluate the interactive effects of alcohol and lead during pregnancy in rats. Our purpose was to see if lead, as lead acetate, would influence the alcohol effect already known to exist. In the first study, pregnant Long-Evans rats received lead (as lead acetate), alcohol (20% w/v), or lead plus alcohol once a day on gestation days (GD) 10-20. On GD 20, when animals were sacrificed, mean blood alcohol levels were consistently higher for the lead-plus-alcohol-dosed groups compared to alcohol alone, but these two groups did not differ in maternal weight gain, percent resorptions, litter size, or fetal weight. Mean blood lead levels were not consistently higher in the lead-plus-alcohol groups compared to lead only, but the lead-plus-alcohol groups differed significantly from the lead-only groups at higher doses in the previously mentioned parameters. The lead-only groups did not differ from vehicle controls in any parameter in spite of blood lead levels as high as 300 micrograms/dl. In the second experiment, animals given a combination of alcohol and lead did not differ in activity, passive avoidance, or active avoidance learning compared to animals given alcohol or lead alone. Animals given lead only or the combination of lead plus alcohol had longer first trial latencies in the passive avoidance test. The data indicate that neither lead nor alcohol attenuates or potentiates each other's effects on reproduction or learning behavior in the Long-Evans rat even at high blood lead levels.

Effect of low-dose lead acetate exposure on the metabolism of nucleic acids and lipids in cerebellum and hippocampus of rat during postnatal development.

Abstract: Postnatal exposure (from the second day after birth to 30 days) of rat pups to low levels of lead acetate (50 mg/kg body weight/day), administered by gastric intubation, yielded a maximum blood level of 76.1 micrograms/100 ml, at day 15 of age. Cerebellar and hippocampal lead contents were 8.67 micrograms/100 mg and 11.7 micrograms/100 mg, respectively, at day 30 of age. This lead exposure has been shown to elicit little change in some biochemical parameters in cerebellum and hippocampus. At the three ages investigated (5, 15, and 30 days after birth) there were no alterations of body weight; brain, cerebellum, and hippocampus wet weight; and DNA, RNA, protein and phospholipid content, either in total tissue or in mitochondria. A similar invariance following lead exposure was observed in mitochondrial succinate dehydrogenase and cytochrome oxidase activities. After intraperitoneal administration, the incorporation of [methyl-14C]thymidine into DNA and [5,6-3H]uridine into RNA of cerebellum and hippocampus showed a significant decrease only at day 5, reaching the control value at 15 and 30 days of age. After intraperitoneal injection, [2-3H]glycerol incorporation into total lipids and phospholipids of cerebellum and hippocampus also showed no significant changes in Pb-treated pups compared to controls at all three postnatal ages. We concluded that subclinical lead administration exerts its effect by slowing cell proliferation in the very early growth phase of the brain. It is likely that a metabolic compensative response to subtoxic effect of lead acetate may be brought about in cerebellum and hippocampus during critical phases of nervous system development between days 15 and 30.

Transplacental Effect of Lead Compounds on Tissue Plasminogen Activator Activity, Plasminogen Activator Inhibition and Plasmin Inhibition

Abstract: The transplacental effect of lead compounds (lead acetate and tetraethyl lead) on the tissue plasminogen activator activity (PAA), plasminogen activator inhibition (PAI) and plasmin inhibition (PI) was studied in the rat. The concentration of lead in organs of the newborn showed a great variation; the distribution of lead in the organs studied depended on the dose and the stage of gestation at injection. In each organ the concentration of lead was dose-dependent. In control specimens no lead could be detected. The tissue response of PAA, PAI and PI to the lead compounds also showed a great variation; however, there was no correlation between lead concentrations and PAA, PAI or PI responses. Changes of one or more of the parameters studied (PAA, PAI or PI) were noticed in lungs, liver, heart, brain and kidneys. The PAA was due to the tissue type plasminogen activator in all organs studied; in kidneys and lungs the urokinase type of plasminogen activator was also detected. Therefore, fetal tissue PAA, PAI and PI can be affected transplacentally by lead compounds.

Nmr Spectroscopic Investigations of Pbtio3 Sol-Gel Processing

Abstract: Lead titanate gels were prepared by sol-gel processing from lead acetate and titanium isopropoxide in methoxyethanol. In the present study, 1H, and 13C FTNMR spectroscopic and mass spectrometric techniques were used to identify the structures of lead and titanium precursors formed by refluxing lead acetate and titanium isopropoxide in methoxyethanol, respectively. Lead acetate was found to be partially alkoxylated, whereas, the titanium precursor was identified as a dimer with complete alkoxy group exchange. Similar procedures were applied to identify the lead titanium complex formed from lead and titanium precursors.

Promoting effect of basic lead acetate administration on the tumorigenesis of lung in N-nitrosodimethylamine-treated mice.

Abstract: Lead compounds are frequent environmental contaminations and some of them have been found to be carcinogenic for animals, although epidemiological studies have not been considered to provide sufficient evidence that exposure to lead or lead compounds causes cancer in humans There re only a few reports on the promoting effect of lead on chemical carcinogenesis in vivo By the concurrent administration of lead compounds and certain organic carcinogens to rats or hamsters, the cocarcinogenic activity of lead has been found in the kidney of rats or the lung of hamsters In this report the promoting effect of posttreatment with basic lead acetate (BLA) on the development of lung tumors in strain dd mice exposed to N-nitrosodimethylamine (NDMA) was examined The concentration of lead and the activity of {gamma}-glutamyltranspeptidase ({gamma}-GTP) in the lung during the carcinogenicity experiment were also measured

Inorganic elements in the tooth and bone tissues of rats bearing nickel acetate- and lead acetate-induced tumors.

Abstract: Biological effects of such metals as nickel and chromium alloys used as dental materials, particularly their metabolism and potential toxicity have not been well elucidated. Certain metallic materials are known to be toxic and arsenic, nickel, chromium and lead have been shown to have carcinogenic potential in laboratory animals. This study was performed to assess carcinogenicity and accumulation in tissues of metals in rats. Three-week old male F344/NSle rats were injected s. c. with 30 mg/kg of nickel acetate or 60 mg/kg of lead acetate weekly for 5 weeks after 2 weeks of acclimatization, and were followed by observation for 80 weeks. The group treated with lead acetate showed a greater incidence of tumor, compared with the nickel acetate-treated group. Teeth, femora, other bones and neoplastic tissue from tumor-bearing animals were subjected to elemental analysis by spectrophotometry and ICP. High concentrations of Pb were detected in the mandibula, femur and tumor tissue of rats with Pb-induced tumor. In rats with Ni-induced tumor, Ni was not demonstrable in the mandibula, maxilla or tumor tissue and detected in small quantities in the nasal bone and femur. Thus, Pb proved to be retained in tissue at the site of injection and also markedly accumulated in the tooth and femur as assessed 46 weeks after injections; whereas Ni was no longer detectable in tissue at the injection site, nor in tumor tissue but only small quantities in the said bones.