Biomonitoring of industrial dusts on animals. I. Bioaccumulation of dust components

The bioaccumulation of industrial dust components in laboratory animals exposed by inhalation was studied under environmental conditions. Three types of industrial emissions were investigated: magnesite emissions, wastes from nickel refinery and cement emissions, respectively. The findings revealed that the chemical components of the industrial dust particles inhaled by animals are accumulated not only in the lungs, but also in the other organs, bone and hair of the exposed animals. In addition, the dust components were found in the organs of the F1 generation as well. This suggests a new aspect for the assessment of the biohazard of industrial dust particles in the environment.     

Electromagnetic fields from mobile phones do not affect the inner auditory system of Sprague-Dawley rats

The auditory system is the first biological structure facing the electromagnetic fields emitted by mobile phones. The aim of this study was to evaluate the cochlear functionality of Sprague-Dawley rats exposed to electromagnetic fields at the typical frequencies of GSM mobile phones (900 and 1800 MHz) by distortion product otoacoustic emissions, which are a well-known indicator of the status of the cochlea's outer hair cells. A population of 48 rats was divided into exposed and sham-exposed groups. Three sets of four loop antennas, one for sham-exposed animals and two for exposed animals, were used for the local exposures. Rats were exposed 2 h/day, 5 days/week for 4 weeks at a local SAR of 2 W/kg in the ear. Distortion product otoacoustic emissions tests were carried out before, during and after the exposure. The analysis of the data shows no statistically significant differences between the audiological signals recorded for the different groups.     

Chromosome damage in rat pulmonary alveolar macrophages following ozone inhalation

To determine whether ozone is clastogenic at environmentally relevant exposure levels, rats were exposed for 6 h to 0.0, 0.12, 0.27, or 0.80 ppm ozone. The alveolar macrophages were isolated from animals sacrificed 28 h after the end of the exposure. The mitotic index and frequency of chromosome aberrations were determined. No change in the mitotic index was detected following 0.12 ppm ozone exposure. A significant decrease in mitotic index was observed after exposure to 0.27 ppm ozone; a significant (4-fold) increase in the frequency of dividing macrophages was detected following exposure to 0.8 ppm ozone. Only chromatid-type aberrations were observed. There was a significant increase in the frequency of cells with chromatid gaps and in the frequency of cells with chromatid deletions. Animals exposed to 0.27 ppm ozone had the highest proportion of cells with chromatid deletions (0.172) relative to background level (0.028). No exchanges or chromosome-type aberrations were detected in any of the animals. These data suggest that ozone, at relatively low levels, is clastogenic in macrophages from exposed rats.     

Effects of exposure to a 60-kV/m, 60-Hz electric field on the social behavior of baboons.

We found in a previously reported study that exposure to a 30-kV/m, 60-Hz electric field had significant effects on the social behavior of baboons. However, it was not established whether or not the effects were related specifically to the 30-kV/m intensity of the field. A new experiment was conducted to determine whether or not exposure to a 60-Hz electric field at 60 kV/m would produce like changes in the baboons' social behavior. We exposed one group of eight male baboons to an electric field 12 hours a day, 7 days a week, for 6 weeks. A second group of eight animals was maintained under sham-exposure (control) conditions. Rates of performing on each of six categories of social behavior and on four categories of nonsocial behavior were used as criteria for comparing exposed with unexposed subjects and for within-group comparisons during three six-week experimental periods: Pre-Exposure, Exposure, and Post-Exposure. The results indicate that (1) during the exposure period, exposed animals exhibited statistically significant differences from controls in means of performance rates based on several behavioral categories; (2) across all three periods, within-group comparisons revealed that behaviors of exposed baboons were significantly affected by exposure to the electric field; (3) changes in performance levels probably reflect a stress response to the electric field; and (4) the means of response rates of animals exposed at 60 kV/m were higher, but not double, those of animals exposed at 30 kV/m. As in the 30-kV/m experiment, animals exposed at 60 kV/m exhibited significant differences in performances of Passive Affinity, Tension, and Stereotypy. Mean rates of performing these categories were 122% (Passive Affinity), 48% (Tension), and 40% (Stereotypy) higher in the exposed group than in the control group during exposure to the 60-kV/m field.     

Changes of insulin binding in rat tissues after exposure to stress.

The effects of various stressors on insulin receptors in adipose, liver and skeletal muscle tissues were studied in rats exposed to acute or repeated stress. Adult male rats were exposed to immobilization (IMO) for 2.5 hours daily for 1, 7 and 42 days, or to hypokinesia (HK) for 1, 7 and 21 days. We determined the values of specific insulin binding (SIB) and insulin receptor binding capacity (IR) of plasma cell membranes from adipose, liver and muscle tissue (IMO groups), or insulin binding to isolated adipocytes and hepatocytes (HK groups). A significant decrease of SIB and IR was observed in rats exposed to acute stress (1x IMO) in muscle, adipose and liver tissues. However, in animals exposed to repeated stress (7x and 42x IMO), SIB and IR were diminished in the muscle tissue, whereas no significant changes were noted in the liver and adipose tissue. When tissue samples were collected 3-24 hours after exposure to IMO stress, no changes of SIB and IR were found in liver and adipose tissue, but insulin binding was lowered in skeletal muscles. In animals exposed to HK for one day, a decrease of SIB and IR was found in isolated adipocytes, but no changes in insulin binding were noted in the liver tissue. In rats exposed to HK for 7 and 21 days, values of IR were similar as in control group. Our results indicate a) the different changes of IR in the liver, fat and muscle tissues after exposure to stress situations, b) a long-term decrease of insulin binding in muscles of rats exposed to repeated IMO stress, and c) the return of reduced SIB and IR (induced by acute stress) to control values in the liver and adipose tissue after a short recovery period.     

Iron kinetics effects of 88 millirads. Partial-versus-total body X-irradiation

Rats were irradiated with one tibia shielded (95% marrow exposure), total body exposed (TBI, 100%), and only one tibia exposed (5%), or they were sham irradiated (SI, 0%). Plasma Fe-59 clearance time (T1/2) and Fe-59 content ratio in the right and left tibia (RT/LT) were assayed to determine the erythroid activity of the overall marrow of the animals and the relative marrow activity in the exposed and shielded tibias, respectively. When a major fraction of the overall marrow was shielded or irradiated, the overall erythroid activity levels were identical to those of the SI and TBI animals, respectively. Interestingly, enhanced normoblastosis was observed in the marrow of the exposed tibia of individual animals exhibiting normal erythroid activity in 95% of the marrow. Conversely, localized marrow with normal erythroid activity was found in a shielded tibia of individual rats, demonstrating an enhanced erythroid activity in a major fraction of the total body. It was concluded that 88 mrad can alter marrow functions in a small isolated skeletal region as effectively as in the whole body, and tandem assays of the Fe-59 T1/2 and Fe-59 RT/LT can facilitate ultra-low-dose X-ray studies involved with partial body exposures.     

Biologic effects of prolonged exposure to ELF electromagnetic fields in rats. I. 50 Hz electric fields

A three-year investigation was conducted on the biological effects of high-intensity electric field exposures of rats for up to 18% of their life span. Two hundred and forty adult male rats, divided into groups of 20 animals each, were exposed at ground potential for 8 h/ day at 25-kV/m and 100-kV/m 50-Hz electric fields or were sham exposed for 280, 440, and 1240 h. The corresponding ages at sacrifice were 140, 164, and 315 days. An additional group of 40 rats was investigated under similar experimental conditions after 440 h of exposure at floating potential. Independent of exposure duration, mode of grounding, and field strength, no statistical differences in body weight, morphology, and histology of the liver, heart, mesenteric lymph nodes, and blood variables (hematology and serum chemistry) were found in comparison with sham-exposed animals. Plasma levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone (TS)at sacrifice varied widely among experimental animals in the same group but did not differ in exposed compared with sham-exposed rats. A nonsignificant tendency toward a decrease in the testes/body weight ratio was found after 1240 h of exposure. Microscopic examination of a large number of specimens showed no quantitative or qualitative statistical differences in testes alterations either among exposed animals or between exposed and their corresponding sham-exposed groups. We conclude that 50-Hz electric field exposure, even of long duration at very high field strengths, does not induce harmful effects on tissues with high cellular turnover rates and does not impair the reproductive function of rats. Moreover, after exposure, all variables investigated were well within the normal physiological range. © 1993 Wiley-Liss. Inc.     

Mutagenicity of 1,3-butadiene at the Hprt locus of T-lymphocytes following inhalation exposures of female mice and rats.

The species specific response to 1,3-butadiene (BD), an important industrial chemical, was investigated by determining the influence of exposure duration and exposure concentration on the mutagenicity of BD in mice and rats and by defining the spectra of mutations in the Hprt gene T-cell mutants from control and BD-exposed mice. Female B6C3F1 mice and F344 rats (4-5 weeks old) were exposed by inhalation to 0, 20, 62.5, or 625 ppm of BD for up to 4 weeks (6 h/day, 5 days/week). Groups of control and exposed animals (n=4-12/group) were necropsied at multiple time points after exposure and the T-cell cloning assay was used to measure Hprt mutant frequencies in lymphocytes isolated from spleen. Mutant clones collected from control and BD-exposed mice were propagated and analyzed by RT-PCR to produce Hprt cDNA for sequencing. In animals necropsied 4 weeks after 2 or 4 weeks of BD exposure (0 or 625 ppm), the rate of accumulation of mutations was greater in mice than in rats. Supra-linear dose-response curves were observed in BD-exposed mice, indicating a higher efficiency of mutant induction at lower concentrations of BD. The mutagenic potency estimates (represented by the differences in the areas under the mutant T-cell 'manifestation' curves of treated vs. control animals) in mice were 11 and 61 following 4 weeks of exposures to 62.5 and 625 ppm of BD, respectively, while mutant frequencies (Mfs) in rats were significantly increased only at 625 ppm BD (mutagenic potency of 7). Molecular analysis of Hprt cDNA from expanded T-cell clones from control and BD-exposed mice demonstrated an increased frequency of mutants in exposed animals that likely contain large deletions in the Hprt gene (P=0.016). These data indicate that both exposure duration and exposure concentration are important in determining the magnitude of mutagenic response to BD, and that mutagenic and carcinogenic properties of BD in mice may be related more to the ability of its metabolites to cause chromosomal deletions than to produce point mutations.     

Possible combined effects of 900 MHZ continuous-wave electromagnetic fields and gentamicin on the auditory system of rats

The aim of this study was to evaluate the cochlear functionality of Sprague-Dawley rats exposed to electromagnetic fields at 900 MHz and to gentamicin by distortion product otoacoustic emissions, which are a well-known indicator of the status of the cochlea's outer hair cells. A population of 32 rats was divided into four groups: group 1 was treated with daily intramuscular injections of 150 mg/kg body weight gentamicin for 15 days; group 2 was treated with daily intramuscular injections of 150 mg/kg body weight gentamicin for 15 days and exposed to electromagnetic fields; group 3 was exposed to electromagnetic fields; group 4 was sham-exposed. Rats were exposed 2 h/day, 5 days/week for 4 weeks at a local SAR of 4 W/kg in the ear (continuous wave at 900 MHz). Distortion product otoacoustic emissions tests were carried out before, during and after the combined exposure. The analysis of the data showed no subchronic exposure to electromagnetic fields on the inner auditory system of rats in either normal ears or ears exposed to a well-recognized pathological agent.     

Effects of whole-body 50-Hz magnetic field exposure on mouse Leydig cells

The main goal of this study was to evaluate the possible effect of whole-body magnetic field (MF) exposure on the steroidogenic capacity of Leydig cells in vitro. In four separate experiments, male CFLP mice were exposed to sinusoidal 50-Hz, 100-microT MF. The duration of exposure was 23.5 h/day over a period of 14 days. At the end of the exposure, interstitial (Leydig) cells were isolated from the testicles of the sham-exposed and exposed animals. The cells were cultured for 48 h in the presence or absence of 1, 10, or 100 mIU/ml human chorionic gonadotropin (hCG). The luteinizing hormone (LH) analog hCG was used to check the testosterone (T) response of the sham-exposed controls and to evaluate the possible effect of the whole-body MF exposure on the steroidogenic capacity of Leydig cells in vitro. Testosterone content of the culture media and blood sera was measured by radioimmunoassay (RIA). In the cultures obtained from MF-exposed animals, the hCG-stimulated T response was significantly higher (p < 0.01) compared with the sham-exposed controls, while the basal T production of cells and the level of serum T remained unaltered. No MF exposure-related histopathological alterations were found in testicles, epididymes, adrenals, prostates, and pituitary glands. The MF exposure did not affect the animal growth rate and the observed hematologic and serum chemical variables. Our results indicate a presumably direct effect of whole-body MF exposure on the hCG-stimulated steroidogenic response of mouse Leydig cells.     

Influence of alternating extremely low frequency ELF magnetic field on structure and function of pancreas in rats.

The aim of this study was to estimate the influence on ultrastructure and function of endocrine and excretoric part of pancreas in rats of extremely low frequency alternating magnetic fields with parameters used in therapy in humans. The animals from the two experimental groups were exposed to a rectangular magnetic field waveform at a frequency of 10 Hz and induction of 1.8-3.8 mT--(group P) or a sinusoidal magnetic field at a frequency of 40 Hz and induction of 1.3-2.7 mT--(group S), respectively. The control rats were subjected to sham exposure. The cycle of 1, 3, 6, 9, and 14 daily exposure sessions lasting 30 min was made in all groups. Some of rats after finishing the cycle of 14 exposures were left in the same conditions except for the magnetic field for 3 or 10 days. In both groups of rats exposed to magnetic field, a distinct tendency to decrease glucose concentration, compared to control group, was observed during the exposure cycle. Serum glucose became normal after the end of exposure sessions. The concentrations of insulin in both groups of rats exposed to magnetic field were significantly higher, compared to the controls, during the exposure cycle. After the end of exposure cycle the concentration of insulin in group S became normal. In contrast, in group P the concentration of insulin decreased significantly on the last day of exposure, with a subsequent increase in the following days. The activity of alpha-amylase and lipase in the serum of experimental and control rats was not affected. In both groups of exposed rats, reversible changes of ultrastructure of the pancreatic islets, including expansion of the Golgi apparatus, extension of rough endoplasmatic reticulum, mitochondrial swelling, expansion of beta-granules and increase in number of empty vesicles in beta cells, occurred during the exposure. In acinar cells of exposed animals, a slight extension of rough endoplasmatic reticulum and mitochondrial swelling as transitory changes were observed. The structural and functional changes in pancreas are probably adaptative ones.     

Environmental influence on ovulation and embryonic development in Rana pipiens.

Environmental effects on ovulation and embryogenesis in Rana pipiens were assessed using both freshly-captured fall animals and laboratory-conditioned females which had undergone vitellogenesis in the laboratory. Frogs in both categories were divided into two groups. Ovulation was hormonally induced in one group of females prior to cold exposure and in the second group of animals following an 8-week-period at 4 degrees C with an 8L 16D photoperiod. The incidence of both ovulation and normal embryonic development was increased following exposure of the animals to low temperatures and short daylength. Those animals which only partially ovulated prior to cold treatment did not respond to hormone injections following the period of cold exposure. Examination of the ovaries of these females revealed a much greater degree of oocyte resorption than was found in frogs whose initial ovulation was induced only after exposure to cold temperatures. The administration of ovulation-inducing hormones prior to artificial hibernation may thus have initiated a phase of oocyte resorption which progressed even at 4 degrees C. The incidence of ovulation was similar in wild-caught and laboratory-conditioned females, but eggs from the latter showed a much lower percentage of development to Shumway stage 20. This effect may have been related to differences in the environmental factors to whcih the two groups were exposed during oogenesis.     

Effect of age and hypoxia on beta-adrenergic receptors in rat heart.

Previous reports suggest that hypoxia downregulates cardiac beta-adrenergic receptors from young rats. Because aging alters response to stress, we hypothesized an age-related alteration in the response to hypoxia. Male Fischer-344 rats, aged 3 and 20 mo, were divided into control and hypoxic groups. The hypoxic rats were exposed to hypobaric hypoxia (0.5 atm) for 3 wk. After hypoxic exposure, body weight decreased, hematocrit increased, right ventricular weight increased, and left ventricular weight decreased in all animals. beta-Adrenergic receptor density declined after hypoxic exposure in the young but not in the older animals, a change that was confined to the left ventricle. beta-Adrenergic receptor density in the right ventricle was significantly lower in the older animals than in the young animals. Plasma catecholamines (norepinephrine, epinephrine) drawn after the animals were killed (stress levels) decreased in young rats and increased in old rats after the exposure to hypoxia. Hypoxia is a useful physiological stress that elucidates age-related changes in cardiac beta-adrenergic receptor and catecholamine regulation that have not previously been described.     

The role of Haemophilus somnus in bovine early embryonic death. III. The effect of the organism on embryos by day 21 postbreeding

A study using 11 healthy, mature Holstein-Friesian heifers was designed to determine whether 1) H. somnus induces gross and/or histopathological changes of the uterine tract and embryos, 2) H. somnus has a short and/or long-term effect on the ovarian activity, 3) prior exposure to H. somnus would modulate the effect of a second exposure to the organism. Superovulated heifers were artificially iseminated 12 and 24 h after standing estrus using high-quality, Haemophilus-free semen from a single ejaculate of one bull. Control heifers (Group 1, n = 2) were infused by intrauterine route, 12 h after the second insemination, with 10 ml of 0.85% sterile phosphate buffered saline (PBS) as a placebo. The treatment heifers were exposed by intrauterine infusion, 12 h after the second insemination, to approximately 1.5 x 10(9)H. somnus organisms (Iowa strain 1229) suspended in 10 ml of 0.85% sterile PBS. Group 2 (n = 2) treatment heifers were exposed 21 d prior to embryo recovery; Group 3 treatment heifers (n = 3) were exposed 5 mo prior to embryo collection; and Group 4 treatment heifers were exposed twice, 5 mo apart with the second exposure 21 d prior to embryo recovery. All animals were slaughtered and the whole genital tract was removed for pathological examination and embryo recovery. There were minimal pathological changes in the uterus. However, H. somnus significantly affected (P 相似文献   

Induction of cadmium-thionein in isolated rat liver cells.

The uptake of cadmium by isolated liver cells was linearly related to the cadmium concentration to which the cells were exposed in the medium. Cadmium-treated cells synthesized proteins de novo with the characteristics of cadmium-thionein induced in the liver of cadmium-treated animals. Thionein from liver cells incorporated cadmium and [35S]cysteine, had a Ve/Vo (Sephadex G-50) of 1.8-1.9, and was separated into two subfractions by DEAE-cellulose ion-exchange chromatography. Cycloheximide and actinomycin D when added after a cadmium exposure prevented the synthesis of thionein. However, addition of actinomycin D after synthesis had started only decreased the total amount of thionein synthesized. The concentration of cadmium to which the cells were exposed affected the amount of cadmium-thionein synthesized in 6h. The maximum response occurred when cells were exposed to 0.5 microgram of cadmium/ml; at higher metal concentrations the total amount of cadmium-thionein synthesized declined. The system described in the present paper can be used to study the mode of metal toxicity and the mechanism of cadmium-thionein synthesis.     

Zinc-, copper- and cadmium-binding protein in Ehrlich ascites tumour cells.

The properties of Ehrlich ascites tumour cells exposed in vivo to cadmium were investigated as a function of the zinc status of the host animals. Tumour-cell growth was inhibited by cadmium in both zinc-sufficient and zinc-deficient animals. However, cells in zinc-sufficient tumours accumulate much less cadmium than those in deficient tumours. The subcellular distributions of cadmium and zinc do not depend on zinc status. Cadmium and zinc are bound to a low-molecular-weight protein with properties similar to metallothionein. Without exposure to cadmium, a zinc- and copper-binding protein is still present that behaves like a metallothionein. This protein can rapidly bind cadmium added to Ehrlich cells in vitro. It is shown that the zinc- and copper-binding protein contains free thiol groups. Ehrlich cells isolated from cadmium-treated animals are viable and show normal incorporation of uridine into RNA, but the cellular uptake of thymidine and its incorporation into DNA are inhibited.     

Effects of 2.45 GHz microwaves on meiotic chromosomes of male CBA/CAY mice

Male CBA/CAY mice were exposed daily (6 days a week) for 30 minutes in an environmentally controlled waveguide to continuous 2.45 GHz microwave radiation for 2 weeks at average whole body absorbed dose rates of 0.05, 0.5, 10, and 20 mW/g. Shan exposed animals served as controls. Chain translocations were observed at diakinesis at metaphase I in microwave exposed animals. The yield of translocations increased with exposure, and varied nonlinearly with dose rate. An increase in incidence of univalents was seen after exposure at 10 and 20 mW/g. The findings are interpreted to indicate interference with normal spermatogenesis during the exposure period.     

Changes in pulmonary surfactant and phosphatidylcholine metabolism in rats exposed to chrysotile asbestos dust.

1.Pulmonary surfactant was isolated from rats that had been exposed to chrysotile asbestos dust for from 3 days to 15 weeks. 2. Asbestos-treated rats showed a progressive increase in amounts of surfactant. After 15 weeks, treated animals contained 4 times as much as non-treated. 3. No significant change was seen in the total protein or total fatty acid composition of surfactant with exposure. 4. The increase in surfactant phosphatidylcholine normally seen on maturation of rat lung was accelerated by exposure of animals to asbestos. 5. An increase in the activity of phosphorylcholine glyceride transferase in lung homogenates and free cell populations was found. 6. Lysosomal phospholipase A was relatively unaffected by dust exposure. 7. It is suggested that the increase in surfactant amounts could be due to an increase in its synthesis without a corresponding alteration in its degradation.     

The influence of maternal nicotine exposure on neonatal lung carbohydrate metabolism.

The influence of maternal nicotine exposure (1 mg/kg body mass/day) during pregnancy and lactation on energy metabolism of lung tissue of neonatal rats were investigated. The glucose turnover of the lung tissue of the neonatal rats exposed to nicotine via the placenta and mother's milk was 86.4% higher than that of the controls. Glycolysis was however suppressed by 22.7% (P < 0.01). The adenine nucleotide pool (ATP+ADP+AMP) was 32.8% higher for the lungs of the 3 week old neonates exposed to nicotine than that of the control rat lung. After 4 weeks of nicotine withdrawal glycolysis of those animals exposed to nicotine were still inhibited to the same extent than during exposure. The adenine nucleotide pool was 69.95% higher than that of the controls. It is proposed that the inhibition of glycolysis was due to the high ATP/ADP ratio of the lungs of the nicotine exposed rats.     

Responses of baboons to prolonged hyperoxia: physiology and qualitative pathology.

Cardiopulmonary responses to prolonged hyperoxia and their relationships to the development of lung pathology have not been fully characterized in primates. In this study, circulatory hemodynamics and pulmonary function, vascular permeability, and leukocyte sequestration were measured in male baboons after 100% O2 exposure and related to ultrastructural changes of lung injury by electron microscopy. Three groups of animals were exposed to 100% O2 in an exposure cage for 40, 66, and 80 h, respectively. A fourth group of animals was exposed in a cage for 80 h and then anesthetized and ventilated with 100% O2 for additional time. These animals were exposed for a total duration of 110 h or until death from the injury. Physiological responses to hyperoxia were characterized by decreases in total lung capacity and inspiratory capacity at 80 and 110 h. A significant increase in pulmonary leukocyte accumulation was noted by 80 h. Extravascular lung water and permeability surface-area product increased at 80 and 110 h. Cardiac output and stroke volume also decreased, and systemic vascular resistance increased after 80 and 110 h of hyperoxia. Histopathological changes were present in the lungs of all but the 40-h exposure group. Animals exposed for 66 h showed endothelial injury and neutrophil accumulation. By 80 h, animals showed endothelial cell destruction, interstitial edema, and type I cell injury. At 110 h, animals showed substantial destruction of endothelial and type I epithelial cells, exposure of alveolar basement membrane, congestion of capillaries, and substantial interstitial edema. The data indicate that histological changes by electron microscopy precede physiological responses to hyperoxic pulmonary injury in baboons by as much as 14 h and that the physiological responses to early hyperoxic injury are relatively insensitive to the pathological injury.