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Biomedical subjects

M Vahter

Publications and source records attributed to M Vahter.

At least 91 records · Page 5Linked to original sources
PubMed1984

The effect of methyltransferase inhibition on the metabolism of [74As]arsenite in mice and rabbits.

The effect of periodate-oxidized adenosine (PAD), an inhibitor of certain methyltransferases, on the biotransformation and tissue retention of [74As]arsenite in mice and rabbits was studied. Injection of PAD (100 mumol/kg body wt.), 15-min prior to the injection of [74As]arsenite (0.4 mg As/kg body wt.), resulted in a 25-70% decrease in the production of [74As]dimethylarsinic acid ( [74As]DMA). This implies that S-adenosylmethionine is the methyl-donor in the methylation of inorganic arsenic in vivo. Due to interaction of the unmethylated arsenite with tissue constituents the PAD-treated animals had significantly higher (2-6 times) tissue concentrations of 74As than did the controls. This effect was first observed in the liver, indicating that this organ is the main site of the methylation of arsenic. The increase in the tissue retention due to the PAD-treatment remained also after cessation of the inhibition of methylation. The results can be seen as confirmation that alkylation of inorganic arsenic acts as a detoxification mechanism in mammals.

Adenosine↗
PubMed1984

Embryotoxicity of arsenite and arsenate: distribution in pregnant mice and monkeys and effects on embryonic cells in vitro.

The distribution of 74As-labelled arsenate and arsenite in pregnant mice and a monkey has been studied by autoradiography and gamma counting of isolated tissues, and their in vitro toxicity to a chondrogenic system has been investigated. With both arsenic forms, given as single intravenous injections to the mother, the 74As-arsenic appeared to pass the mouse placenta relatively free and approximately to the same extent. The retention time in maternal tissues including the placenta was, however, around three times longer with arsenite than with arsenate. In early gestation, high activity was registered in the embryonic neuroepithelium, which correlates well with reported CNS malformations in rodents. In late gestation, the distribution pattern was more like that in the adults. Accumulation in skin and squamous epithelia of the upper gastrointestinal tract (oral cavity, oesophagus and oesophageal region of stomach) dominated the distribution picture, especially at a long survival interval. Arsenate, but not arsenite, showed affinity for the calcified areas of the skeleton. A marmoset monkey in late gestation receiving arsenite showed a somewhat lower rate of placental transfer than the mice. Skin and liver had the highest concentrations (at 8 hrs), both in mother and foetuses. This species is known not to methylate arsenic, resulting in stronger binding and longer retention times of arsenic as compared with other species. The stronger binding in maternal tissues may possibly explain the lower rate of placental transfer. Arsenite was shown to inhibit cartilage formation in a chick limb bud mesenchymal spot culture system (ED50 approximately 5-10 microM), while arsenate seemed to be without effect at concentrations up to 200 microM (highest tested). Arsenate, however, showed a potentiation of the arsenite toxicity.

Animals↗
PubMed1983

Intracellular interaction and metabolic fate of arsenite and arsenate in mice and rabbits.

In vitro incubation of [74As]arsenite, -arsenate or -dimethylarsinic acid (DMA, the main metabolite of inorganic arsenic) with liver, lung and kidney homogenate of mice and rabbits showed that arsenite is the main form of arsenic bound to tissues. Injection of arsenite in mice and rabbits (0.04 mg As/kg body wt.) caused higher concentration of arsenic in the liver and the lungs than did the same dose of arsenate. This was less marked in the mice than in the rabbits, mainly due to the faster methylation to DMA. The relatively high degree of binding of arsenic to tissue constituents which also followed injection of arsenate may be explained by in vivo reduction to arsenite. The similar binding pattern after exposure to arsenite and arsenate indicates further that one and the same form of arsenic, arsenite, is retained independent of the form of exposure to inorganic arsenic. In contrast to the liver and lungs the kidneys showed a higher retention of arsenic after injection of arsenate than after injection of arsenite. Following injection of [74As]DMA in the animals excretion was essentially completed within 24 h, indicating low affinity for the tissues in vivo.

Animals↗
PubMed1983

Lead in petrol.

Explore the source record for details and available documents.

Gasoline↗
PubMed1983

Assessment of exposure to lead and cadmium through biological monitoring: results of a UNEP/WHO global study.

This paper describes a UNEP/WHO project on the assessment of human exposure to lead and cadmium through analysis of blood and kidneys. The following countries have participated: Belgium, India, Israel, Japan, Mexico, People's Republic of China, Peru, Sweden, United States, and Yugoslavia. No laboratory started the monitoring before achieving satisfactory results of quality control (QC) analysis (samples of cow blood spiked with lead and cadmium and freeze-dried horse kidney cortex for cadmium analysis) according to predetermined criteria based on a linear regression model. Two hundred teachers from one urban area in each country constituted the target group for lead and cadmium in blood and cases of "sudden, unexpected death" for cadmium in kidney cortex. QC samples were analyzed in parallel with the monitoring samples to assure validity of the obtained results. The quality assurance program also included preanalytical quality control. There was considerable variation in metal exposure between areas. Geometric means for lead in blood ranged from about 60 micrograms Pb/liter in Beijing and Tokyo to 225 in Mexico City. The values were below 100 micrograms Pb/liter also in Baltimore, Jerusalem, Lima, Stockholm, and Zagreb, and between 100 and 200 micrograms Pb/liter in Brussels and India. In general, males had higher blood levels than females and smokers higher than nonsmokers. With a few exceptions the values were lower than results reported in a recent study within the European Communities. Geometric means for cadmium in blood ranged from 0.5 microgram Cd/liter in Stockholm and Jerusalem to 1.2 in Brussels and Tokyo. Cadmium levels were considerably higher among smokers than among nonsmokers. Tokyo had the highest values for cadmium in kidney cortex with a geometric mean in the age group 40-60 years of 60-70 mg Cd/kg wet wt. Lowest values were found in Baltimore, Beijing, India, and Jerusalem, with means around 20-25 mg Cd/kg wet wt. There was a tendency toward higher values for smokers than for nonsmokers, but no differences related to sex. Data were not received from Mexico and Peru.

Animals↗
PubMed1983

In vivo reduction of arsenate in mice and rabbits.

In vivo reduction of AsV, has been studied in mice and rabbits by determination of arsenic metabolites in plasma and urine after administration of [74As]arsenate. The amount of AsIII in bladder urine of mice 1 hr after administration (0.04 or 0.4 mg As/kg body wt) corresponded to 0.4-2.9% of the dose. AsIII was also detected in plasma 1 hr after administration. In rabbits, catheterized in the bladder for continuous collection of urine, about 10% of the administered arsenate (0.04 mg As/kg body wt) was reduced and excreted in form of AsIII during 4 hr after administration, corresponding to about 20% of the total arsenic excreted. Arsenic excreted during the first hour was mainly in form of unmetabolized AsV and some AsIII. Thereafter the excretion of both AsIII and dimethylarsinic acid increased. The results indicated that AsV has to be reduced to AsIII before being methylated.

Animals↗
PubMed1983

Metabolism of arsenobetaine in mice, rats and rabbits.

The distribution, retention and biotransformation of arsenobetaine, the most common organic arsenic compound in fish and crustacea, have been studied in mice, rats and rabbits by use of synthesized 73As-labelled arsenobetaine. Orally administered arsenobetaine was almost completely absorbed from the gastro-intestinal tract in mice. The urinary excretion for 3 days following intravenous injection was about 75% of the dose in the rabbits and more than 98% in the mice and rats. The rate of excretion in mice was independent of the dose level in the range 4 to 400 mg As/kg body weight. In both animal species the tissue distribution differed widely from that observed following exposure to inorganic arsenic. The clearance of arsenobetaine from plasma and most tissues was fast (somewhat faster in mice than in rabbits) and seemed to follow first-order kinetics. The clearance from cartilage, testes, epididymis, and in the rabbits also the muscles, was slower and consisted of more than one phase. 73As-arsenobetaine was the only labelled arsenic compound detected in urine and soluble extract of tissues, indicating that no biotransformation occurred.

Animals↗
PubMed1982

Autoradiographic studies on the distribution of arsenic in mice and hamsters administered 74As-arsenite or -arsenate.

Whole-body autoradiography in combination with other determinations of tissue levels of 74As-arsenic in mice, 5 min. to 30 days after intravenous injections of 74As-arsenite (As III) or -arsenate (As V), showed higher organ concentrations and whole-body retention of arsenic in the As III mice as compared to the As V mice. Only the kidneys (at short time intervals) and the skeleton had higher levels in the As V mice as compared to the As III mice. The skeletal accumulation of As V is probably due to the resemblance of the arsenate to phosphate, so that arsenate may substitute for phosphate in the apatite crystal. The long-term retention of arsenic was most apparent in hair and skin, squamous epithelium of the upper gastrointestinal tract (oral cavity, oesophagus, and the oesophageal part of the stomach mucosa), the epididymis, thyroid, lens and skeleton. The accumulation in hair, skin and the upper gastrointestinal tract may be ascribed to a binding to keratin, the content of which is high in squamous epithelia. The distribution of arsenic in golden hamsters was similar to that found in mice. The significance of the findings in relation to reported adverse effects of inorganic arsenic is discussed.

Animals↗
PubMed1981

A rapid method for the selective analysis of total urinary metabolites of inorganic arsenic.

Total urinary arsenic has traditionally been used for assessing occupational exposure to inorganic arsenic. However, dietary arsenic, especially from seafood, may greatly influence this value. This paper describes a fast and convenient method for routinely measuring the combined amount of inorganic arsenic, methylarsonic acid, and dimethylarsinic acid, which are the major urinary metabolites after exposure to inorganic arsenic. Organic arsenic compounds of marine origin are not biotransformed to inorganic arsenic or methylated arsenic acids to any significance in the human body. They do not produce arsines when treated with the reducing agent in the proposed method and will therefore not interfere with the measurements. The sensitivity, accuracy, and precision of the proposed method are sufficient for the determination of concentrations of arsenic normally found in the urine of nonexposed persons. The method is based on a commercially available hydride generation kit attached to an atomic absorption spectrophotometer.

Arsenic↗
PubMedDate not supplied

Metabolism of methylmercury in rabbits and hamsters.

The metabolism of 203Hg-labeled methylmercury chloride (MeHg) has been studied in rabbits and hamsters. Rabbits were administered 1.6 mumols MeHgCl/kg bw intravenously, and hamsters 40 mumols/kg bw orally. Urine and feces were collected daily and groups of four animals killed after 1 h, 1 d, or 7 d. The concentration of 203Hg in blood, liver, kidney, spleen, lung, heart, and brain was determined by gamma counting. In both animal species, the clearance of 203Hg in the brain was slower than in other tissues. In the rabbits the brain 203Hg concentration increased during the whole experimental period. Rabbits excreted 203Hg primarily in feces (about 20% of the dose within 1 wk), and much less in urine (less than 2%). In contrast, hamsters very efficiently excreted 203Hg in urine (50% in 1 wk). The fecal excretion was similar to that of the rabbits. Separation of inorganic Hg and MeHg in urine from hamsters by ion exchange chromatography showed that about 90% of the urinary 203Hg was excreted as MeHg. These findings show that rabbits and hamsters are interesting experimental animal systems for studying the metabolism of MeHg.

Animals↗
PubMedDate not supplied

Intracellular distribution and chemical forms of arsenic in rabbits exposed to arsenate.

Inhibition of the methylation of arsenic in rabbits by ip injection of periodate-oxidized adenosine (PAD) prior to an iv injection of 74As-arsenate (AsV; 0.4 mg As/kg body wt) caused a marked increase in the retention of 74As in both the cellular organelles and the soluble fractions of liver and kidney. One day after exposure, almost 30% of the arsenic in the liver and about 40% of the arsenic in the kidney was recovered in the nuclear fraction. In the liver nuclei, the inhibition of the methylation increased the 74As content of the insoluble fraction and most of this arsenic was protein-bound. The major part of the soluble intranuclear 74As was in the form of AsIII, formed by reduction of the administered AsV. In the liver, PAD also caused a pronounced increase in the 74As content of the microsomal fraction. In the kidneys, where most of the arsenic was present as AsV, there was a marked accumulation of arsenic in the mitochondria.

Animals↗
PubMedDate not supplied

Demethylation and placental transfer of methyl mercury in the pregnant hamster.

The demethylation and placental transfer of methylmercury (MeHg) was studied in Syrian Golden hamsters administered a single oral dose of 203Hg-labeled MeHgCl, 1.6 mumol/kg body weight, on day 2 or 9 of gestation and sacrificed 1 day before expected parturition. In order to evaluate the role of demethylation for transplacental transport of MeHg, four hamsters were administered 203Hg-labeled HgCl2 intravenously on day 9 of gestation. The mean biological halftime of 203Hg in animals administered radiolabeled MeHg was 7.7 days and the fecal route was the main excretory pathway. The fetal content of 203Hg in hamsters administered radiolabeled MeHg on gestational day 2 or 9 corresponded to 1.3% and 4.6% of the administered dose, respectively. The distribution of 203Hg in the fetus was more even than in the dam and the concentration of 203Hg in the fetal brain, liver and kidney was similar to that of the placenta. Inorganic Hg was found in maternal liver (18% of total Hg), kidney (31%) and placenta (21%) and fetal liver (3%). The amount of inorganic 203Hg in fetal liver corresponded to about 0.015% of the dose administered to the dam as MeHg. When hamsters were administered 203HgCl2 by intravenous injection on day 9 of gestation, the concentration of 203Hg in fetal liver corresponded to 0.03% of the administered dose. The inorganic 203Hg detected in fetal liver after maternal exposure to MeHg was probably due to demethylation of MeHg in the dam and transplacental transfer of inorganic Hg.

Administration, Oral↗
PubMedDate not supplied

Impact of soil and dust lead on children's blood lead in contaminated areas of Sweden.

The impact of lead in soil and dust on blood lead concentrations in young children (i.e., 1-5 y of age, N = 202) and the risk of health effects were investigated in an urban and a mining area of Sweden. Blood, soil, and indoor dust, as well as information on lead-exposure factors, were collected. The blood lead concentrations (total range = 9-77 microg/l) the authors measured indicated a low risk for lead-induced health effects. Lead in soil (i.e., < 10-5,000 microg/g) and in dust (i.e., < 1-316 microg/g) had little effect on blood lead concentrations, given the present conditions and present concentration range--especially in the mining area. Urban children had significantly higher blood lead concentrations than children in the mining area, despite higher concentrations of lead in soil in the mining area. In the urban children, blood lead concentrations were influenced by parental smoking and lead in dust at day-care centers.

Air Pollutants↗
PubMedDate not supplied

Exposure to environmental tobacco smoke in the household and urinary cotinine excretion, heavy metals retention, and lung function.

The relationship between urinary levels of cotinine (U-cotinine) and arsenic (U-As), blood levels of cadmium (B-Cd), blood levels of lead (B-Pb), lung function, and questionnaire data on smoking habits were studied in 107 parents and their 46 children (7-10 y of age). There was a statistically significant relationship between the reported amount of tobacco smoked and U-cotinine levels. Nonsmokers who were married to persons who smoked had three times higher U-cotinine levels than nonsmokers whose spouses did not smoke. There was a significant association between the number of parents who smoked in the family and the U-cotinine levels of children. If only one parent smoked, maternal smoking was of greater importance than paternal smoking. There was also an association between U-cotinine and B-Cd. A study of lung function in the children revealed that vital capacity and functional residual capacity (corrected for sex, age, and height) increased as the number of parents who smoked increased. Therefore, the present study showed that (1) U-cotinine was a useful index of active smoking and environmental tobacco smoke exposure in adults and children, (2) U-cotinine was associated with the blood concentration of cadmium, and (3) environmental tobacco smoke exposure was associated with changes in lung function of children.

Adult↗
PubMedDate not supplied

Personal NO2 exposure monitoring shows high exposure among ice-skating schoolchildren.

A method for measuring personal nitrogen dioxide (NO2) exposure, using passive samplers, was tested among schoolchildren. Activity patterns and NO2 exposure levels were studied in relation to urban and rural living. Stationary air monitoring data indicated that the urban children were supposed to be exposed to NO2 levels that were among the highest in Sweden. It was shown that NO2 levels measured at the stationary air monitoring station were not representative for the children's exposure. The children spent 90% of their time indoors; only a small percentage of their time was spent in transit. The median daily NO2 exposure level in the urban area (13 micrograms NO2/m3, 7 ppb) was significantly higher (p < .001) than in the rural area (7 micrograms NO2/m3, 4 ppb). The most important source of exposure was the indoor ice-skating arenas, where levels up to 8,000 micrograms NO2/m3 (4 240 ppb) were measured during 1-h periods.

Air Pollutants↗