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PubMed1994

Molecular dosimetry of DNA adducts in rainbow trout (Oncorhynchus mykiss) exposed to benzo(a)pyrene by different routes.

Farm raised rainbow trout (Oncorhynchus mykiss) were exposed by various routes to benzo(a)pyrene (BP) as a representative carcinogenic polycyclic aromatic hydrocarbon (PAH). Following exposure of fish to the chemical by intraperitoneal (i.p.) injection, 32P-postlabelling studies indicated that non-feral trout were relatively resistant to the formation of BP-DNA adducts in liver. No adducts were detected in fish exposed to single doses (20 mg/kg) of BP. Multiple exposures (e.g. 2 x 25 mg/kg) were necessary in order for adducts to be detected, indicating that induction of the metabolising enzymes required for the bioactivation of BP is necessary. These studies provided reference information on DNA adducts for comparison with data from subsequent experiments at environmentally realistic low level exposures. Two types of low level aquatic exposure were carried out. The first procedure exposed fish for 30 days to a nominally constant low level (1.2 and 0.4 micrograms/l) of a homogeneous dispersion of BP in water, to simulate low level aquatic environmental exposures. Following 32P-postlabelling analysis of the liver DNA of exposed fish, BP-DNA adducts were not detected. In the second procedure, fish were exposed to a constant low level of BP (ca. 0.5 micrograms/l) for 15 days then to a pulse (60 micrograms/l) which was allowed to naturally decline (to ca. 2 micrograms/l) during a further 15 days. Following this exposure, significant levels of BP-DNA adducts were detected in livers of trout. The effect of dietary exposures was investigated by feeding trout a diet containing either 58 micrograms or 288 micrograms BP per day for 6 days, equivalent to total doses of 43 mg/kg and 216 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed2003

Loss of heterozygosity analysis of mouse pulmonary adenomas induced by coal tar.

Manufactured gas plant (MGP) residues, commonly known as coal tars, were generated several decades ago as a byproduct of residential and industrial gas production from the distillation of coal. Previous short-term exposure studies have shown MGP residues to be tumorigenic in mouse liver and lung. In order to gain further insight into carcinogenesis by complex mixtures of environmental chemicals containing known carcinogenic polycyclic aromatic hydrocarbons, we investigated mouse pulmonary tumors for loss of heterozygosity (LOH) as a result of multiple exposure to MGP residues. Twenty mouse lung adenomas produced in (C57BL/6 x C3H)F1 hybrid mice and manually microdissected were selected to examine genome-wide allelic losses at 58 microsatellite loci. Regions of chromosomes 1, 4, 5, 8, and 11 were affected in 30-40% of tumors. The elevated rates of allelic imbalance in these chromosomes may indicate the location of unknown tumor suppressor genes significant to neoplastic transformation in mouse lung tissues. Laser capture microdissection-based LOH analysis of pulmonary adenomas showed that contamination of nonneoplastic tissues was not masking the allelic losses in the manually microdissected tumor analysis. The low frequency of chromosome instability in these tumors, measured by means of inter-simple sequence repeat PCR, suggests the presence of discrete regions of LOH instead of extensive structural rearrangements.

Adenoma↗
PubMed2006

Pesticides and Parkinson's disease--is there a link?

Parkinson's disease (PD) is an idiopathic disease of the nervous system characterized by progressive tremor, bradykinesia, rigidity, and postural instability. It has been postulated that exogenous toxicants, including pesticides, might be involved in the etiology of PD. In this article we present a comprehensive review of the published epidemiologic and toxicologic literature and critically evaluate whether a relationship exists between pesticide exposure and PD. From the epidemiologic literature, there does appear to be a relatively consistent relationship between pesticide exposure and PD. This relationship appears strongest for exposure to herbicides and insecticides, and after long durations of exposure. Toxicologic data suggest that paraquat and rotenone may have neurotoxic actions that potentially play a role in the development of PD, with limited data for other pesticides. However, both the epidemiology and toxicology studies were limited by methodologic weaknesses. Particular issues of current and future interest include multiple exposures (both pesticides and other exogenous toxicants), developmental exposures, and gene-environment interactions. At present, the weight of evidence is sufficient to conclude that a generic association between pesticide exposure and PD exists but is insufficient for concluding that this is a causal relationship or that such a relationship exists for any particular pesticide compound or combined pesticide and other exogenous toxicant exposure.

Environmental Pollutants↗
PubMed2003

Repeated exposure to blue light does not improve psoriasis.

BACKGROUND: Increased endogenous levels of protoporphyrin IX (PpIX) have been reported in the skin of patients with psoriasis. Activation of PpIX with blue light after exogenous topical application of its precursor, aminolevulinic acid, can improve psoriasis. Light activation of endogenous PpIX for the treatment of psoriasis has never been studied. OBJECTIVE: The purpose of this study was to determine the efficacy of multiple exposures to blue light in patients with plaque psoriasis. METHODS: A total of 17 patients with plaque psoriasis presenting increased endogenous level of PpIX were enrolled. Of the 2 identified plaques on each patient, 1 was exposed to 10 J/cm(2) of blue light from a fluorescent panel 3 times per week for 4 consecutive weeks. Plaque severity was assessed in a blinded fashion. PpIX levels were measured with in vivo fluorescence spectroscopy weekly. RESULTS: A single exposure to blue light induced almost complete photobleaching of PpIX. There was no significant difference between the mean psoriasis severity score of the plaques before and after 12 exposures to blue light. CONCLUSION: Repeated exposure to blue light did not improve psoriasis.

Adult↗
PubMedDate not supplied

The AAPM/RSNA physics tutorial for residents. X-ray generators.

The x-ray generator delivers the electrical power to energize the x-ray tube and permits the selection of x-ray energy, x-ray quantity, and exposure time. Major internal components of the generator include transformers, diodes and rectifier circuits, filament and stator circuits, timer switches, and kilovolt and milliampere meters. Single-phase, three-phase, high-frequency, and constant potential generators produce different voltage waveforms (ripple) and x-ray beam spectra. Phototimer and automatic brightness control subsystems measure radiation exposure incident on the image receptor to give instantaneous feedback for optimal radiographic film densities and fluoroscopic image brightness, respectively. At the generator control console, the operator sets the tube voltage, tube current, exposure time, phototimer film density, spot film acquisition, and fluoroscopic parameters. Selection of generator power and options depends on the intended clinical use. X-ray tube focal spot size and power loading capability should be matched to the x-ray generator and clinical imaging requirements. Single and multiple exposure rating charts as well as anode and housing thermal characteristic charts indicate power input and dissipation rates specific to a generator and x-ray tube target and housing.

Humans↗
PubMed1997

Enhancement of radiation-inducible hepatic glutathione-S-transferases Ya, Yb1, Yb2, Yc1, and Yc2 gene expression by oltipraz: possible role in radioprotection.

Previous studies have shown that radiation in combination with oltipraz enhances hepatic microsomal epoxide hydrolase expression. The effects of gamma-ray radiation exposure in combination with oltipraz on the expression of hepatic glutathione-S-transferase (GST) subunits Ya, Yb1, Yb2, Yc1, and Yc2 were examined in the rat. Northern RNA blot analyses revealed that GST mRNA levels were altered in response to daily 3- or 0.5-Gy doses of radiation. The hepatic GST mRNA levels were transiently decreased at 3 and 8 hr after a single 3-Gy dose of radiation. The GST Ya, Yb1, Yb2, Yc1, and Yc2 mRNA levels were increased by 2-4-fold at 15 and 24 hr after irradiation with 3 Gy, followed by return to the levels of untreated rats at 48 hr after treatment. The treatment of animals with oltipraz alone resulted in dose-related increases in the GST Ya, Yb1, Yc1, and Yc2 mRNA levels, whereas Yb2 mRNA levels were, minimally increased. Although a single dose of oltipraz (30 mg/kg orally) caused a minimal 2-fold elevation in the hepatic GST Ya mRNA level, exposure of animals to both oltipraz and 3-Gy radiation resulted in a 4-fold relative increase in GST Ya mRNA level, indicating that the Ya mRNA expression was additively enhanced by the combination treatment. The Yb1/2 and Yc1/2 mRNA expressions were also enhanced by oltipraz in combination with radiation. Multiple exposure of rats to daily 0.5-Gy radiation caused time-related increases in GST gene expression. The greatest enhancement in GST expression was observed at 24 hr after a single 0.5-Gy dose of radiation in conjunction with oltipraz (e.g., a 9-fold relative increase in GST Ya), whereas the relative additive increases in GST mRNA were less pronounced at day 3 or 5 after treatment. These increases in the GST mRNA levels were consistent with those in the immunochemically detectable GST protein levels. Histopathological examinations revealed that exposure of rats to radiation (0.5 Gy/day for 3-5 days) caused mild-to-moderate hepatocyte degeneration with sinusoidal congestion, whereas oltipraz (30 mg/kg/day for 3 days) was effective in blocking the radiation-induced liver injury. The enhanced expression of these GST isoforms by oltipraz may be associated in part with its hepatoprotective effect against the injury caused by ionizing radiation.

Animals↗
PubMed1986

Peripheral and central nervous system lesions caused by triethyl- and trimethyltin salts in rats.

Both trimethyltin and triethyltin salts are known to produce toxic lesions in the central nervous system. Triethyltin intoxication has been associated with central intramyelin edema, while trimethyltin has been shown to produce neuronal necrosis in selected limbic and sensory regions of the brain. Only scant attention has been paid to peripheral nerves of animals treated with alkyltins. In this study, we have treated rats with 6 or 8 mg/kg trimethyltin, and 1, 2, 4, 6, or 8 mg/kg triethyltin (single or multiple exposure), and evaluated in detail at the light microscope level both central and peripheral nervous system lesions. In addition to the central neuron necrosis or myelin edema described previously, both compounds produced peripheral axon degeneration and chromatolysis of large spinal cord and brain stem neurons. Chromatolysis was seen in reticular neurons of the brain stem and ventral horn or spinal cord in rats receiving high doses (6 or 8 mg/kg) of triethyltin, and in these same areas plus mesencephalic trigeminal nucleus in animals treated with trimethyltin. Wallerian-like degeneration of peripheral axons was seen in sciatic and tibial nerve and ventral roots of animals receiving 3 injections of 4 mg/kg or single or multiple injections of 6 or 8 mg/kg triethyltin. Axon degeneration was also seen in sciatic and tibial nerves 21 days after a single exposure to 8 mg/kg trimethyltin. Since myelin edema is believed to be reversible, the axonal changes described here may be of greater clinical significance in relation to human exposure.

Animals↗
PubMed1999

Radiation exposure during chest X-ray examinations in a premature intensive care unit: phantom studies.

BACKGROUND: There are few reports on the radiation dose received by infants, their family and radiographers exposed to scatter radiation in a premature baby intensive care unit. OBJECTIVE: To evaluate the degree of radiation exposure from diagnostic X-ray examinations with mobile X-ray machines in a premature intensive care unit. MATERIALS AND METHODS: The radiation exposure of an adjacent newborn, the radiographer and other persons in the room was simulated using phantoms during X-ray examination of the chest using vertical and horizontal beams. RESULTS: Most of the measured doses were below the registration limit of the measuring apparatus and had to be extrapolated by multiple exposures. Without exception, the maximal doses were significantly lower than the permitted limit for persons not professionally exposed to X-rays. CONCLUSIONS: Recommendations to avoid unnecessary radiation exposure are given.

Humans↗
PubMed2000

Acute exposure to the abused inhalant, isobutyl nitrite, reduced T cell responsiveness and spleen cellularity.

Isobutyl nitrite is an inhalant abused principally by male homosexuals. We have reported that subchronic inhalation exposure (45 min/day for 14 days) to 900 ppm isobutyl nitrite was immunosuppressive. In the present study, the effects of acute exposure to the inhalant were examined. Mice were exposed in an inhalation chamber to 900 ppm isobutyl nitrite for 45 min. One day later, spleen cellularity was reduced by 39% without selectively depleting CD4(+) or CD8(+) cells. The numbers of peripheral blood leukocytes and peritoneal cells were also reduced. Following acute inhalation exposure, T cell proliferative responses stimulated with allogeneic cells or anti-CD3 and anti-CD28 antibodies were inhibited, while mitogen-induced responses were not affected. Purified T cells exposed to the inhalant also had compromised responses, suggesting a direct effect on T cells. However, the cumulative effects of multiple exposures were necessary to inhibit T-dependent antibody responses or T cell or macrophage cytotoxicity.

Administration, Inhalation↗
PubMed1980

Interaction between environmental pollutants and respiratory infections.

The major aspects that must be considered in studies of the health effects of environmental pollutants are: the direct damage due to the exposure, the role of pre-existing disease, and effects of the exposure on the response to secondary stresses. In experimental studies at concentrations of air pollutants found in urban environments frank toxicological responses are rarely observed. However, exposure to a secondary stress, i.e. respiratory challenge with infectious bacteria, can exacerbate the response of the experimental host. Changes in the resistance to respiratory infections provide a highly sensitive experimental animal model system, which is increasingly used in studies of health effects of air pollutants. This model indicates the impairment of the basic defense mechanisms of the respiratory system by the combined exposure to low concentrations of pollutants and the superimposed bacterial infection. Changes in the resistance to respiratory infections were studied in various species of laboratory animals. S. pyogenes and K. pneumoniae are the bacteria of choice to induce the pulmonary infection. Included in the studies are short-term single and multiple exposures as well as long-term exposures to gaseous pollutants such as O3 and NO2 and particulate pollutants such as sulfates and nitrates. Changes in the resistance are measured as excess mortalities and reduced survival time as compared to those in infected animals not exposed to the pollutants. Other parameters measured ranged from changes in the immune response to changes in retention rates of bacteria in lungs.

Aerosols↗
PubMedDate not supplied

The morphologic spectrum of halothane-induced hepatic injury: analysis of 77 cases.

Hepatic histopathology and clinical-pathologic correlations were studied in 77 patients who met clinical criteria for halothane hepatotoxicity. They were divided into groups based on the type of surgery (minor or major) and outcome (nonfatal, biopsy group or fatal, autopsy group). The two nonfatal groups (minor surgery and major surgery) and the two fatal groups (minor surgery and major surgery) were comparable with regard to age, time of onset from exposure, peak aminotransferase values and peak bilirubin determinations. A spectrum of histologic patterns was identified in these patients. It ranged from panlobular and multifocal spotty necrosis resembling viral hepatitis through submassive confluent zonal necrosis to massive necrosis. Progression of severity of injury from spotty to massive necrosis was more closely related to multiple exposures to halothane (and especially repeated exposure within less than three months), than to the extensiveness of the associated surgical procedures.

Adult↗
PubMed1977

Proliferative response of human diploid fibroblasts to intermittent light exposure.

Three- to four-hour exposure to fluorescent light, one to three times weekly, reproducibly enhanced the proliferation rate of human diploid fibroblasts. This enhancement was observed in WI-38 and a line from whole embryo mince at late population doubling level (PDL) as well as in a line from adult skin at early PDL. Single or multiple exposures of short duration stimulated proliferation, whereas exposures of long duration were cytotoxic. This proliferative response is reversible, and is mediated through the culture medium, Dulbecco Vogt's supplemented with 10% fetal bovine serum. Apparently light produces some mitogenic substance(s) in the culture medium that accumulates in the cells and is toxic or growth-stimulatory depending on its concentration per cell. Another possibility is that light produces in the medium both cytotoxic and growth-stimulatory substances.

Cell Division↗
PubMedDate not supplied

Synergism of methylmercury and selenium producing enhanced antibody formation in mice.

Mice fed 1, 5, and 10 ppm methylmercury plus 6 ppm selenium for 10 wk had a significant increase in antibody synthesis. Since methylmercury singly depresses antibody synthesis and the response was greater than that produced by selenium alone, synergism between methylmercury and selenium occurred. In this case, the synergism is considered to be advantageous to a host, while exposure by other combinations of environmental contaminants may be detrimental. Mercury concentrations in the kidney were markedly elevated when methylmercury and selenium were administered simultaneously compared to when methylmercury was given without selenium supplement. These results indicate that data collected from individual pollutants may not be of value in predicting responses to multiple exposure.

Animals↗
PubMed1988

The effect of exposure regimen and duration on benzene-induced bone-marrow damage in mice. I. Sex comparison in DBA/2 mice.

In the mouse, the concurrent evaluation of micronuclei frequencies in peripheral blood polychromatic erythrocytes (PCE) and normochromatic erythrocytes (NCE) permits an assessment of both recently-induced and chronically-accumulated bone-marrow damage. This assay system was used to evaluate on a weekly basis the effect of exposure duration (1-13 weeks, 6 h per day) and exposure regimen (Regimen 1:5 exposure days per week; Regimen 2:3 exposure days per week) on the ability of 300 ppm benzene to induce genotoxic damage in the bone marrow of male and female DBA/2 mice. In addition, an analysis of the percentage of PCE in peripheral blood was used to evaluate benzene-induced alterations in the rate of erythropoiesis. Exposure to benzene induced a marked increase in the frequency of micronucleated PCE (MN-PCE), an effect which was considerably greater in male mice than in female mice. In both sexes, the induction of MN-PCE was independent of exposure regiment and of exposure duration. Exposure to benzene also resulted in an exposure duration-dependent increase in the frequency of MN-NCE. The frequency of MN-NCE increased more slowly in female than in male mice and, within each sex, more slowly in Regimen 2 animals. Apparent steady-state conditions for MN-NCE frequencies were attained by about the fifth week of exposure in female mice exposed by either regimen and in male mice exposed by Regimen 2. Steady-state conditions for MN-NCE frequencies in male mice exposed to benzene by Regimen 1 did not occur during the duration of the study. An analysis of %PCE data revealed an initial severe depression in the rate of erythropoiesis in both sexes, with the return in the production of PCE to control levels being dependent on both sex and exposure regimen. Suppression of PCE production occurred throughout the course of the study in Regimen 2 males, while the percentage of PCE returned to control levels sporadically after 5 weeks in Regimen 1 males and within 5 weeks in females, regardless of regimen. Thus, while the sex-dependent induction of genotoxic damage by multiple exposures to benzene over a 13-week period was independent of exposure regimen and duration, the induction of cytotoxic damage was both sex- and regimen-dependent. The most severe depression of erythropoiesis occurred in male DBA/2 mice exposed to benzene by the more intermittent regimen (i.e., 3 days/week versus 5 days/week).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1981

Effects of exposure to peroxyacetyl nitrate on susceptibility to acute and chronic bacterial infection.

A significant increase in mortality due to acute respiratory pneumonia caused by inhalation of Streptococcus pyogenes aerosol was seen after a single 3-h exposure of mice to 14.8-28.4 mg/m3 peroxyacetyl nitrate (PAN). The excess mortality ranged from 8 to 39% and the decrease in survival time from 2.4 to 7.9 d. A single exposure to 25.0 mg/m3 PAN resulted in a significant increase in total number of cells lavaged from the lungs but somewhat decreased levels of adenosine triphosphate (ATP) in alveolar macrophages. Exposure to 7.4 mg/m3 PAN for 3 h/d, 5 d/wk, for 2 wk resulted in a reduced total count of free pulmonary cells and a significant reduction of ATP levels in alveolar macrophages but had no effect on mortality or survival rate. Scanning electron microscopic observations of the respiratory tract after both single and multiple exposures to PAN showed raised and sloughing nonciliated cells in the nasal cavities and tracheas and presence of excess mucus. Six daily 3-h exposures to 25.0 mg/m3 PAN did not produce any marked changes in a chronic respiratory infection in mice as measured by Mycobacterium tuberculosis lung titers.

Acetates↗
PubMed2003

Squire's Quest! Dietary outcome evaluation of a multimedia game.

BACKGROUND: Fruit, juice, and vegetable (FJV) consumption among children is low. Innovative programs are needed to enable children to increase FJV intake. Psychoeducational multimedia permits the delivery of interventions as designed and capitalizes on known behavior change principles. DESIGN: Elementary school was the unit of recruitment, assignment, and analysis. Twenty-six elementary schools were pair matched on size and percentage of free or reduced-price lunch, and randomly assigned to treatment or control groups. Data were collected just before and just after the program. SETTING/PARTICIPANTS: All fourth-grade students in participating elementary schools were invited to participate. Data were collected on 1578 students. MAIN OUTCOME Servings of fruit, 100% juice, and vegetables consumed. INTERVENTION: Squire's Quest! is a ten-session, psychoeducational, multimedia game delivered over 5 weeks, with each session lasting about 25 minutes. Based on social cognitive theory, educational activities attempted to increase preferences for FJV through multiple exposures and associating fun with their consumption, increase asking behaviors for FJV at home and while eating out, and increase skills in FJV preparation through making virtual recipes. MEASURES: Four days of dietary intake were assessed before and after the intervention. Assessment was made by the Food Intake Recording Software System (FIRSSt), which conducts a multiple pass, 24-hour dietary intake interview directly with the children. RESULTS: Children participating in Squire's Quest! increased their FJV consumption by 1.0 servings more than the children not receiving the program. CONCLUSIONS: Psychoeducational multimedia games have the potential to substantially change dietary behavior. More research is warranted.

Beverages↗
PubMed2006

Rat brain DNA transcript profile of halothane and isoflurane exposure.

Inhaled anesthetics produce many effects and bind to a large number of brain proteins, but it is not yet clear if this is accompanied by widespread changes in gene expression of the biological targets. Such changes in expression might implicate functionally important targets from the large pool of binding targets. Both rats and isolated primary cortical neurons were exposed to anesthetics and DNA oligonucleotide microarrays were used to detect and quantify transcriptional changes in neural tissue. Using analysis of variance with multiple testing correction, multiple exposures of rats to 0.8 MAC (minimum alveolar concentration) halothane only produced significant changes in a few metabolic genes. No significant in-vivo gene transcriptional response to 0.8 MAC isoflurane was detected. The use of primary cortical neurons allowed exposure to 3 MAC anesthetics without evidence of toxicity. Isoflurane altered several genes involved with neurotransmitter transport, signaling and cellular structure, whereas halothane produced few detectable changes in these cultured cells. Selected genes were confirmed by quantitative reverse transcription-polymerase chain reaction. Although indicating only a small degree of transcriptional regulation, these data implicate several plausible targets, including synaptic vesicle handling, that might contribute to drug action. In addition, the data show different gene expression profiles for the two inhaled anesthetics, suggesting unique pharmacological targets and mechanisms in each case.

Anesthetics, Inhalation↗
PubMedDate not supplied

Ozone, air pollution, and respiratory health.

Of the outdoor air pollutants regulated by the Clean Air Act of 1970 (and recently revised in 1990), ozone has been the one pollutant most difficult to control within the federal standards. The known human health effects are all on the respiratory system. At concentrations of ozone which occur during summer air-pollution episodes in many urban metropolitan areas of the United States, a portion of the healthy population is likely to experience symptoms and reversible effects on lung function, particularly if exercising heavily outdoors. More prolonged increase in airway responsiveness and the presence of inflammatory cells and mediators in the airway lining fluid may also result from these naturally occurring exposures. Serial exposures to peak levels of ozone on several consecutive days are more characteristic of pollution episodes in the Northeast United States and may be associated with recurrent symptoms. No "high-risk" or more sensitive group has been found, in contrast to the case of sulfur dioxide, to which asthmatics are more susceptible than normals. The occurrence of multiple exposure episodes within a single year over many years in some areas of California has led to studies looking for chronic effects of ozone exposure on the lung. To date, no conclusive studies have been reported, although further work is under way. Much of what we know about the effects of this gas on the lung are based on controlled exposures to pure gas within an environmental exposure laboratory. Interactions between substances which commonly co-occur in air-pollution episodes are also under investigation.

Air Pollution↗