Rabbit alveolar macrophages after inhalation of soluble cadmium,cobalt, and copper: A comparison with the effects of soluble nickel

Rabbits were exposed to aerosols of chlorides of cadmium, copper, and cobalt (0.4–0.6 mg/m³ as metal) for 1 month (5 days/week and 6 hr/day). The effects on alveolar macrophages were compared with earlier reported effects of nickel chloride (0.3 mg/m³ as Ni). Effects of Cd²⁺ exposure resembled those of Ni²⁺ exposure. The number of macrophages in lavage fluid and the variance of cell diameters were thus increased and many cells contained lamellated inclusions. Contrary to macrophages from Ni²⁺-exposed rabbits, the surface of about 50% of the cells had cytoplasmic blebs. However, such cells were rarely seen by scanning electron microscopy. There were significantly more polymorphonucleated neutrophils and small lymphocytes, suggesting lung parenchymal damage. Cells from Cd²⁺-exposed animals, like cells from Ni²⁺-exposed ones, showed an increased oxidative metabolic activity after stimulation with Esherichia coli bacteria. Bactericidal capacity, on the other hand, tended to be enhanced rather than decreased, as in the nickel experiment. After Co²⁺ exposure, the number of macrophages was slightly increased in the lavage fluid and the cells showed an increased metabolic activity both at rest and upon stimulation with bacteria. Cu²⁺ exposure gave a slight increase in lamellated inclusions in the macrophages.     

Social activation of the elderly: A social experiment

Social isolation and understimulation are considered to be major problems among institutionalized aged. This article describes an ‘activation’ program for elderly people living in a senior citizen apartment building. The intention of the research team was to devise a program together with the elderly and the staff, the goals being to increase social activation and self-dependence among the alderly. The program devised was implemented within the apartment's existing financial framework, involving no additional costs, overtime work or external resources. The program was designed in such a way as to allow for measurement of social activation in both the experimental and control groups. This report focuses primarily on the problems which arose in the personnel group in conjunction with the program. Evaluation of these problems was carried out by means of tape-recorded personnel meetings. This paper presents the analysis of these recordings. It was of major importance to the program that any organizational changes be enacted only on the initiative of the elderly and the staff themselves. The results show that it is possible, with relatively simple and inexpensive methods, to stimulate the elderly's interests and counteract social isolation and understimulation.     

Sister chromatid exchange in response to variations in occupational lead exposure

Sister chromatid exchange (SCE) rates in 10 long-term lead-exposed men increased significantly with increasing zinc protoporphyrin concentration in blood. SCE rates were also related to blood lead levels, but this correlation was not statistically significant. These results were obtained before the summer vacation. Six men were examined again shortly after the vacation; both SCE rates and lead-exposure parameters had decreased significantly. An increase was seen in one worker; however, this result could be related to a serious disease for which he was undergoing treatment. Continued examinations showed a tendency of increasing SCE rates and exposure parameters, but the follow-up was too incomplete to allow a statistical analysis. Further studies of 18 newly employed workers failed to show any increase in SCE during the first 4 months of employment despite some increases in both zinc protoporphyrin and lead levels in the blood. The results obtained suggest that a genotoxic effect due to inorganic lead may occur in long-term lead-exposed workers.     

Short-term test for predicting the potential of xenobiotics to impair reproductive success in fish

Short-term screening tests with the zebra fish (Brachydanio rerio) have been developed for predicting the potential of xenobiotics to impair reproductive success in fish. The aim was to find simple and sensitive test parameters and to simulate exposure situations typical for anadromous fish species (salmonids), which generally cross heavily polluted coastal areas or estuaries before they reach uncontaminated upstream spawning areas. Therefore, particular attention was directed to tests designed to assess adverse effects induced during gametogenesis in adult fish. the test protocol involves exposure of adults prior to, but not during, spawning and the effects are measured in the offspring as alterations in hatching frequency and hatching rate of eggs, and survival and stress tolerance of embryos and larvae. Some representative examples of the application of these tests are given, and it is shown that impairment of reproductive success can be induced by exposure of parent fish prior to spawning at concentrations of xenobiotics at least five times lower than those yielding effects during direct exposure of embryos and larvae. It is suggested that, in hazard assessment programs, tests of the effect of xenobiotics on the offspring of preexposed adults be routinely incorporated.     

Clusters of malformations in Sweden: A study with central registers

Clustering of malformations and especially of spina bifida in Sweden was studied using the Register of Malformations and the Medical Birth Records Register. The incentive to this study was provided by the observation of a cluster of malformations, notably spina bifida, and perinatal deaths, locally thought to be related to the use of herbicides in forestry. This cluster was verified but it was shown that a high rate of spina bifida existed in the region before the introduction of herbicides in forestry. Some other clusters of spina bifida were identified and also a number of clusters of other malformations. Case-history studies were performed but revealed no lead to an explanation. Principles in the origin of the clusters and their analysis are discussed.     

The influence of surfactants on gill physiology and cadmium uptake in perfused rainbow trout gills

Cadmium transfer through and the retention of metal in perfused gills from rainbow trout (Salmo gairdneri) has been studied in the presence of two detergents, LAS (linear alkylaryl sulphonate) and NP-10EO (nonylphenol ethoxylate). Accordingly, the effects of the metal and the surfactants on gill viability (vascular resistance, oxygen diffusion capacity, sodium net flux) was measured. Cd had no effect on gill viability either at 0.008 or at 9.0 mumol/liter during a 60-min perfusion period. The viability of the gills deteriorated markedly during 60 min of exposure to 100 mumol/liter LAS and to NP-10EO, or to a mixture of 100 mumol/liter surfactant + 8.1-8.3 mumol/liter Cd. LAS, 100 mumol/liter, reduced Cd transfer, whereas NP-10EO had no effect. NP-10EO increased Cd retention in gill tissue. LAS more than doubled Cd transfer through the gills when tested in concentrations expected to be found in a polluted recipient (0.9 micrograms/liter Cd + 0.05 mg/liter LAS). NP-10EO had no effect on the transfer when tested under these environmentally relevant conditions.     

Mutagen sensitivity, smoking habits and enzyme induction in healthy middle-aged men

Unscheduled DNA synthesis (UDS) (excision-repair) of N-acetoxy-2-acetylaminofluorene (NA-AAF) damage to the DNA of human lymphocytes and levels of ³H-labeled NA-AAF bound to the DNA (carcinogen binding) of lymphocytes after 18 hr of culturing were measured in a consecutive subsample of healthy middle-aged males attending a multiphasic health screening program at the Department of Preventive Medicine in Malmö during 3 weeks in November-December 1981, and compared relative to their smoking habits, body weight, serum cholesterol, and γ-glutamyltransferase levels as well as aryl hydrocarbon hydroxylase inducibility. This study group numbered 66 males and was uniform in sex, age, and investigation time. No case of significant arterial hypertension was present. The UDS and carcinogen binding results showed no correlation with the other factors measured, with the exception of smoking which was strongly (P < 0.01) associated with increasing levels of both the UDS and carcinogen binding values. It is concluded that under ordinary circumstances smoking may represent the most important exogenous factor which may modulate risk to cardiovascular disease and cancer by influencing individual mutagen sensitivity.     

Behavioural and endocrine reactions in boys scoring high on Sennton neurotic scale viewing an exciting and partly violent movie and the importance of social support

Psychoendocrine and behavioural effects elicited by viewing an exciting and partly violent movie were studied in 12-year-old boys (n = 42). The boys were divided into three groups. Group A (n = 13) consisted of boys scoring below the median value on the Sennton neurotic scale for vegetative and anxiety symptoms. Group B (n = 13) consisted of boys scoring above the median value on the Sennton neurotic scale. None of these boys had ever visited a psychiatric treatment centre, and they all came from the same school. A third group, Group C (n = 16), consisted of boys who, at least once, had visited an out-patient clinic at a child psychiatric treatment centre for neurotic problems. These boys attended different schools in the hospital catchment area. Group C had the same mean score on the Sennton neurotic scale as did Group B. By having two groups of boys scoring both high on the Sennton neurotic scale, one of which knew the other boys and one that did not, we were able to study possible effects of social support on psychobiologic reactions in neurotic boys. The boys' reactions to the movie were assessed by: self-ratings; direct observations of the boys by a team of trained child psychologists; and by analysis of urinary output of adrenaline, noradrenaline and cortisol. Group B rated their experience the strongest, viewing the movie, while Groups A and C rated themselves as rather unaffected by it. Group C was rated less verbally active, both during the control and the film periods, than were the other two groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of paraquat on plasma glucose, cortisol, catecholamines, and insulin in the beagle

Paraquat is known to produce hyperglycemia in rodents, although the mechanisms responsible for the hyperglycemic effect of paraquat are not clearly understood. In this study we report the effects of paraquat (25 mg/kg iv) on plasma glucose, cortisol, catecholamines, and insulin in dogs. Paraquat caused a significant increase in plasma glucose level at all times of measurement except at 0.5 hr following paraquat administration. The cortisol levels after paraquat treatment were increased to 133, 305, 279, 418, 517, 672, and 567% above zero time control at 0.5, 1.5, 3, 6, 12, and 24 hr, and at death time respectively. The catecholamines at these times were increased to 42, 17, 72, 118, 138, 226, and 435% above the control. In contrast to cortisol and catecholamines, the plasma insulin levels after paraquat treatment were significantly decreased at 3, 6, 12, and 24 hr. These hormonal observations can explain, at least in part, the observed hyperglycemia, since all promote hyperglycemic states. For example, cortisol is gluconeogenic, catecholamines are glycogenolytic, and lower insulin levels result in depressed peripheral glucose utilization.     

Deviations in ornithine-related metabolism during hexachlorocyclohexane-induced hepatocarcinogenesis in mice: evidence for conversion of glutamate to ornithine

Chronic administration of technical-grade hexachlorocyclohexane in Swiss male mice resulted in necrosis, and later in adenomatous nodules and hepatocellular carcinomas at 3, 7, and 10 months, respectively, after initiation of the experiment. A definite pattern of changes were observed of arginase, ornithine transaminase, ornithine carbamoyltransferase activities, and metabolites related to ornithine. Conversion of glutamate to ornithine correlated well with the decreased glutamate and constant ornithine in liver of mice fed hexachlorocyclohexane for 7 months.     

Psychological, sociological and health behaviour aspects of a long term activation programme for institutionalized elderly people

The present study deals with psychological, sociological and subjective health aspects of social isolation and understimulation in institutional elderly people. In a controlled study over a 6 month period, A programme was devised in collaboration with residents of a senior citizens apartment building and its staff. The aim of the programme was to increase social activation and to encourage among the elderly an enhanced control over their daily lives. It was agreed that the programme implemented should involve no extra costs, overtime work or external resources. Most psychological and sociological variables were stable over the 6 month period. However, social activity level increased 3-fold in the Experimental group compared with the Control group. The E-group also started to attend activities outside the actual programme, and in general spent more time out of doors. Seasonal variations were found in feelings of depression, visits to the country/summer houses, as well as visits by children and neighbours. There were no changes in psychosomatic or psychological complaints indices. However, feelings of restlessness decreased significantly in the E-group over the 6 month period compared with the C-group. There was also a non significant decrease over time in complaints of heart palpitations in the E-group.     

Subcellular distribution of lead in cultured rat hepatocytes

A clear understanding of the sequence and molecular mechanism of the events involved in lead toxicity is hampered by a lack of information about lead compartmentation within the cell. As part of a continuing effort to identify the mechanism by which lead affects cellular functions, we examined the subcellular distribution of ²¹⁰Pb in cultured hepatocytes. The cells were isolated, labeled, homogenized in sucrose-N-[(2-hydroxyethyl)piperazine]-N′-2-ethanesulfonic acid buffer, and fractionated into mitochondrial, microsomal, and cytosolic components by differential centrifugation. Complete fractionation of the cells revealed that 71% of the cellular ²¹⁰Pb was associated with the mitochondria, 5% with the microsomes, and 24% with the cytosol. A modified, rapid fractionation procedure indicated that 45% of the cellular lead was associated with both the mitochondria and the cytosol and 10% with the microsomes. When the cells were separated into total particulates and cytosol with a single centrifugation, 22% of the ²¹⁰Pb was associated with the soluble fraction. The process of homogenization and fractionation of the isolated hepatocytes altered the intracellular distribution of ²¹⁰Pb. This experimental approach to studying the localization of lead may be compromised by the redistribution of ²¹⁰Pb during the extensive centrifugations and resuspensions required for subcellular fractionation and suggests that the subcellular distribution patterns of ²¹⁰Pb obtained by the fractionation of cells reflects the distribution of lead in the homogenate rather than the distribution of ²¹⁰Pb in the intact cell.     

Concentrations of lead in the soft tissues of male rats during a long-term dietary exposure

Newborn rats of albino Wistar strain were exposed to lead from birth, first indirectly through maternal milk and then directly through a diet containing 0.5% lead acetate. At 3, 6, and 12 months of age some of the male rats were killed for the determination of the concentrations of lead in the blood, brain, kidneys, and liver. This long-term exposure resulted in a slight retardation of growth, yet no change in the food consumption was seen. Concentrations of lead in the blood and brain were similar at 3 and 6 months of age, but significantly higher at 12 months, while the concentrations of lead in the kidneys increased significantly with age. Of the brain parts examined the forebrain had the highest concentration of lead, which increased significantly with age. The present study, together with already published data, demonstrated clearly that lead accumulated in rat brain during the suckling period remains relatively unchanged throughout adult life, while the concentrations in the blood and other soft tissues fall rapidly after weaning. Thus the blood lead level cannot be used as a measure of the amount of lead in the brain, particularly in the case of long-term or intermittent exposure of the young.     

Factors affecting plasma benzo[a]pyrene levels in environmental studies

Benzo[a]pyrene (BaP) is a useful indicator of exposure to polycyclic aromatic hydrocarbons (PAHs), airborne carcinogenic compounds. Radioimmunoassay was used to test for plasma BaP differences in 61 subjects divided into three groups based on geographic-demographic locale: urban-industrial, urban-residential, and outer suburban. The results showed that the urban-industrial area participants had a significantly higher mean plasma BaP level than did the outer suburban subjects. The urban-residential subjects did not have a significantly different mean plasma benzo[a]pyrene level from either of the other two groups. Obesity, as measured by Quetelet's index, was found to have a significant correlation with BaP levels. These results indicate that radioimmunoassay of plasma for BaP may be used successfully to judge environmental exposure to PAHs, provided physiological considerations such as obesity are taken into account.     

Incorporation of [3H]uridine into RNA under the influence of dieldrin and polychlorinated biphenyls.

The present study was conducted to determine the influence of two organochlorines, i.e., polychlorinated biphenyl (Aroclor 1242) and dieldrin, or RNA synthesis in elicited peritoneal macrophages. Tritiated uridine ([³H]uridine) incorporation into RNA was used as an index of RNA synthesis. RNA synthesis was depressed in macrophages incubated in the presence of dieldrin in both a time- and dose-related manner. The dieldrin-induced inhibition of RNA synthesis was further exacerbated when the macrophages were actively phagocytosing latex particles. Aroclor 1242 similarly inhibited RNA synthesis in resting macrophages; however, inhibition was not seen until a concentration exceeding 7 ppm of Aroclor 1242 was used in the incubation medium. Dieldrin-induced inhibition of RNA synthesis was observed at levels of 1 ppm. The inhibition of RNA synthesis provides a corroborative index to support the hypothesis previously advanced that the observed in vivo organochlorine-induced immune suppression may be macrophage mediated. Since the observed in vivo immune suppression was manifested in the absence of any morphological changes in the target lymphoid-macrophage tissues, a biochemical lesion, perhaps at the level of RNA synthesis, may be a site for the organochlorine-induced immunosuppression.     

Mesothelioma in pet dogs associated with exposure of their owners to asbestos

Pet dogs with spontaneous mesothelioma were used to identify environmental exposures that might increase their owner's risk of asbestos-related disease. These animals share man's domicile environment, yet do not indulge in activities (e.g., smoking, working) which confound interpretation of epidemiologic studies. Eighteen histologically confirmed canine mesotheliomas were diagnosed at the Veterinary Hospital of the University of Pennsylvania, Philadelphia, from April 1977 to December 1981. Sixteen owners of cases and 32 owners of age, breed, and sex-matched controls were interviewed to determine their occupation and medical history and their dog's medical history, life style, diet, and exposure to asbestos. An asbestos-related occupation or hobby of a household member and use of flea repellents on the dog were significantly associated with mesothelioma. In addition, there was a trend indicating an increased risk of mesothelioma with an urban residence. Lung tissue from three dogs with mesothelioma and one dog with squamous cell carcinoma of the lung had higher levels of chrysotile asbestos fibers than lung tissue from control dogs. These findings indicate that well-designed epidemiological studies of spontaneous tumors in pet animals may provide insight into the role of environmental factors in human cancers and serve as a valuable sentinel model to identify environmental health hazards for humans.     

Metabolism, excretion, and tissue distribution of [14C]photodieldrin in nonhuman primates following oral administration and intravenous injection.

Metabolism, excretion, and body distribution of [¹⁴C]photodieldrin were studied in the rhesus monkey (Macaca mulatta) after single intravenous and repeated oral administration. After iv administration about 45 and 34% of the dose were excreted by the male and the female, respectively, during 21 days following dosing. Approximately two-thirds of the excreted radioactivity was detected in the urine. The body distribution showed high concentrations of photodieldrin and/or metabolites in adipose tissue, liver, bile, bone marrow, mesenteric lymph nodes, and adrenal cortex. Analysis of feces and urine showed the presence of several metabolites. The major metabolite was identified by mass spectrometry, infrared spectrometry, and gas chromatographical comparison as trans-photoaldrindiol which appears in the urine as glucuronic acid conjugate and as free metabolite. A second metabolite, occurring in feces and urine, appears to be a monohydroxy substituted derivative of photodieldrin.     

Interaction of cadmium chloride and γ irradiation on blood parameters of the young adult rat

Two hundred and sixteen male Sprague-Dawley (S-D) rats, 80 ± 5 days old and weighing 220–250 g each, were assigned at random to nine groups of 24 rats each. Rats were injected with cadmium (Cd) intraperitoneally every 3 days for 29 days for a total of nine injections. Injections doses were 0, 1.0, or 2.5 mg Cd kg^?1 body wt. Twenty-four hours after the last Cd injection (Day 30), each rat received an acute whole-body ⁶⁰Co γ radiation dose of 0, 3.62, or 5.43 Gray (Gy) at a dose rate of 33.04 Gy min^?1. The irradiated groups exhibited significant decreases in the total number of white blood cells (WBCs) and the percentage of lymphocytes. Significant increases were seen in the percentage of polyneutrophils, serum triacylglycerols (TG), serum iron, and serum lactate dehydrogenase (LDH). Cd-treated groups had increased total WBCs, percentage of polyneutrophils, and serum glutamate oxaloacetate transaminase (SGOT). Significant decreases were observed in the percentage of lymphocytes, hemoglobin, total number of red blood cells (RBCs), and hematocrit. In the co-insult, significant decreases were seen in the total number of WBCs and RBCs, the percentage of lymphocytes, hemoglobin, and hematocrit. Significant increases were observed in the percentage of polyneutrophils and serum iron. In general, Cd acted as a debilitator which enhanced the overall effect of ionizing radiation when applied as the second insult. On the other hand, Cd also provided protection against radiation; that is, some parameters such as total WBCs, serum TG, serum iron, and serum LDH were not as adversely affected by the co-insult as when radiation only was used. The mechanism of this Cd anomaly is not known.     

Identification of carcinogens by measurement of cell-mediated immunity. IV. Antitumor immunity following perinatal exposure to 1,2-dimethylhydrazine

This study was initiated to investigate the possible perinatal carcinogenic effects of the colon carcinogen 1,2-dimethylhydrazine (DMH) in Fischer F344 inbred rats. Pregnant female animals during their 16-18th day of gestation were administered the chemical by intraperitoneal injections, and beginning at 4 months postparturition, the antitumor cell-mediated immunity (CMI) was delineated in the dams and pups as an indirect measure of carcinogenesis. The CMI status was established by the ability of peripheral blood lymphoid cells obtained from the rats to injure and kill target tumor cells derived from an X-ray-induced rat small bowel adenocarcinoma cell line with the degree of damage being reflected in the quantity of loss of radioiodinated peripheral and integral membrane proteins from the target cells. A significant antitumor CMI was observed in the exposed offsprings although there was no apparent difference between the immunoresponsiveness observed in either the males or the female siblings. Unexpectedly, the mothers exhibited little such antitumor cellular immunity following the carcinogenic insult; even though all previous investigations of adult animals always demonstrated such an immunological response following exposure to the quantities of DMH that were administered (0.1 to 20 mg per kg body wt). As a consequence, these findings tentatively implied that the state of pregnancy alters a female's response to chemical carcinogenic insults and may actually serve as a device for protection from environmentally caused cancer. The threshold detection level for DMH exposure utilizing immune measurements was found to be approximately 10 times smaller for the perinatal susceptibility to the chemical insult intimating that such tests might usefully be incorporated in those bioassays utilized for determining the cancer-causing potential of weak carcinogens. Our findings now suggest that DMH may indeed be a perinatal carcinogen and that immune responsiveness may be readily employed for identifying such substances. However, the definitive studies of actually identifying cancer following such in utero exposures remain to be accomplished.