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1. |
Mercuric chloride affects protein secretion in rat primary hepatocyte cultures: A biochemical ultrastructural, and gold immunocytochemical study |
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Journal of Toxicology and Environmental Health,
Volume 38,
Issue 4,
1993,
Page 343-354
Mario Lachapelle,
France Guertin,
Michel Marion,
Michel Fournier,
Francine Denizeau,
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摘要:
The toxicity of mercury on hepatocytes was studied at the ultrastructural, biochemical, and immunocytochemical levels. Albumin metabolism was examined because it is a representative liver‐specific function. A novel cytochemical method using the protein A‐gold technique for the in situ localization of albumin in hepatocyte cultures was applied. Primary rat hepatocyte cultures were exposed to increasing HgCI2concentrations. Cytotoxicity was assessed by measuring the release of lactic dehydro‐genase from the cells. At the highest exposure concentration tested (50 μM), Hg was found to be significantly cytotoxic in contrast to what occurred at 5.0 and 0.5 μM. The level of albumin secreted, as measured by ELISA, was decreased by approximately 38% at 5.0 μMHgCI2and was found not to be different from that of controls at lower concentrations. The ultrastructural analysis showed that hepatocytes treated with 5.0 μMHgCI2undergo drastic morphological changes such as a decreased number of ribosomes associated with the rough endoplasmic reticulum, and the disappearance of the latter organelle, proliferation of the smooth endoplasmic reticulum, and dilatation of both the Colgi apparatus and the biliary canaliculus‐like structures. Immunocytochemical detection of albumin‐immunoreactive sites using protein A‐gold labeling further revealed that these were less abundant in hepatocytes treated with 5.0 μMHgCI2(—64%) as compared to control preparations. These results suggest that one of the effects of mercury on hepatocytes is to affect liver‐specific functions such as albumin production, possibly through interference with ribosomal function. This study also demonstrates for the first time the applicability of the high‐resolution protein A‐gold technique for toxicological investigations on hepatocytes in vitro.
ISSN:0098-4108
DOI:10.1080/15287399109531723
出版商:Taylor & Francis Group
年代:1993
数据来源: Taylor
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2. |
Absorption of polycyclic aromatic hydrocarbons through human skin: Differences between anatomical sites and individuals |
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Journal of Toxicology and Environmental Health,
Volume 38,
Issue 4,
1993,
Page 355-368
J.G.M. VanRooij,
J.H.C. De Roos,
M.M. Bodelier‐Bade,
F.J. Jongeneelen,
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摘要:
In order to determine differences in absorption of polycyclic aromatic hydrocarbons (PAH) between anatomical sites and individuals, coal‐tar ointment was applied to skin of volunteers at various sites. The surface disappearance of PAH and the excretion of urinary 1‐OH‐pyrene after skin application of coal‐tar ointment were used as parameters for dermal PAH absorption. The surface disappearance was determined by the measurement of the fluorescence of PAH on skin.
ISSN:0098-4108
DOI:10.1080/15287399309531724
出版商:Taylor & Francis Group
年代:1993
数据来源: Taylor
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3. |
Effect of pyrldine on the hepatic and pulmonary metabolism of 2‐butanol in rat and rabbit |
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Journal of Toxicology and Environmental Health,
Volume 38,
Issue 4,
1993,
Page 369-379
DonaldA. Page,
GaryP. Carlson,
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摘要:
Pyridine has been shown to be an effective inducer of the ethanol‐inducible cytochrome P‐450IIE1 in both liver and lung. The oxidation of 2‐butanol by rat liver is inducible by chronic ethanol consumption. The purpose of this study was to determine the effect of pyridine on the hepatic and pulmonary metabolism of butanol. Comparisons were made between rat and rabbit. Acute pyridine treatment (200 mg/kg, ip) increased hepatic metabolism of 2‐butanol in the rat twofold and in the rabbit threefold. The effect of pyridine on hepatic butanol oxidase is similar to the effect reported by other investigators for ethanol administered in the drinking water for 3 wk. Control rabbit pulmonary butanol oxidase activity was 10‐fold higher than that in the rat. Pyridine decreased pulmonary butanol oxidase activity in the rabbit. The effect was demonstrated both in vitro and in the isolated perfused rabbit lung. Pyridine had no effect on pulmonary butanol oxidase activity in the rat.
ISSN:0098-4108
DOI:10.1080/15287399309531725
出版商:Taylor & Francis Group
年代:1993
数据来源: Taylor
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4. |
Recovery potential of hepatocytes from inhibition of albumin secretion by cadmium |
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Journal of Toxicology and Environmental Health,
Volume 38,
Issue 4,
1993,
Page 381-392
Xiamei Wan,
Mario Lachapelle,
Michel Marion,
Michel Fournier,
Francine Denizeau,
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摘要:
The aim of this study was to examine albumin production, a typical liver‐specific function, in hepatocytes treated with Cd and to examine the reversibility of the perturbations induced by the toxic metal. Cultures of freshly isolated rat hepatocytes were exposed to increasing amounts of Cd in modified Leibowitz L‐15 medium for 20 h; the cells were then allowed to recover by further incubation in Cd‐free medium for an additional period of 20 h. The levels of albumin secreted into the extracellular medium were determined by enzyme‐linked immunosorbent assay and were found to be reduced by Cd in a concentration‐dependent fashion over the first 20 h. Inhibition was seen at Cd concentrations that did not cause any loss of cellular viability (up to 0.5 μM Cd), as judged from the release of lactate dehydrogenase by the cells. After replacement of the exposure medium by Cd‐free medium, the same pattern of diminished albumin secretion was obtained, revealing the persistence of the cytotoxic effects when recovery conditions were applied. Moreover, hepatocytes exposed to 0.5 μM Cd for 20 h and processed for visualization of albumin immunoreactive sites using protein A‐gold and electron microscopy exhibited very low albumin‐specific labeling as compared to the controls (0.6 ± 0.05 vs. 20.0 ± 2.6 gold particles/μm2). Intracellular glutathione levels were not significantly changed by Cd either after the initial exposure or after the incubation that followed in control medium. The accumulation of Cd by the cells, as measured by graphite furnace atomic absorption spectrophotometry, was concentration dependent. It remained stable after medium change, indicating that Cd efflux was negligible upon reestablishment of normal conditions. The present data show that the perturbations in albumin metabolism caused by Cd are not readily alleviated after the cells are returned to Cd‐free medium, suggesting a limited short‐term recovery potential against cytotoxic damage. The data also demonstrate that hepatocyte‐specific functions can be used as sensitive indicators for the detection of cellular disturbances by hepatotoxins.
ISSN:0098-4108
DOI:10.1080/15287399309531726
出版商:Taylor & Francis Group
年代:1993
数据来源: Taylor
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5. |
Toxicological effects of ziram, thiram, and dithane M‐45 assessed by sperm shape abnormalities in mice |
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Journal of Toxicology and Environmental Health,
Volume 38,
Issue 4,
1993,
Page 393-398
E. Hemavathi,
M. A. Rahiman,
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摘要:
The three commonly used dithiocarbamate fungicides ziram, thiram, and dithane M‐45 were investigated for their mutagenic and carcinogenic potency using sperm shape abnormalities in mice. The fungicides were administered intraperitoneally in single and cumulative doses. All three of the fungicides tested were found to induce significant increase in the frequency of abnormal sperm at all the doses, and a linear dose effect was observed.
ISSN:0098-4108
DOI:10.1080/15287399309531727
出版商:Taylor & Francis Group
年代:1993
数据来源: Taylor
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6. |
Influence of the dose levels of cocarcinogen ferric oxide on the metabolism of benzo[a]pyrene by pulmonary alveolar macrophages in suspension culture |
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Journal of Toxicology and Environmental Health,
Volume 38,
Issue 4,
1993,
Page 399-417
A. L. Greife,
D. Warshawsky,
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摘要:
The concurrent administration of a cocarcinogenic carrier particle such as ferric oxide (Fe2O3)and the polycyclic aromatic hydrocarbon lung carcinogen benzo[a]pyrene (BaP) results in a decreased latency and an increased incidence in the production of lung tumors in hamsters compared to the administration of BaP alone. The pulmonary alveolar macrophage (AM), the primary lung defense cell, has been shown to endocytize BaP, metabolize BaP to a more biologically active form, and then release the metabolites. Therefore, a study was undertaken to determine in a dose‐response manner the effect of AM phagocytosis of a carrier particle (Fe2O3)on the metabolism of a carcinogen (BaP) and on the production of reactive oxygen. The AM were lavaged from hamsters and cultured in suspension (2.5 x 106cells/vial) with BaP (62.5 nmol,14C labeled) alone or adsorbed onto 0.5, 1.0, or 2.0 mg Fe2O3in the presence of cytochromec. Following separate ethyl acetate extractions of the AM and medium, the metabolites were isolated by high‐performance liquid chromatography (HPLC) and quantified by liquid scintillation spectrometry. The production of superoxide anions was monitored by the reduction of cytochromec.
ISSN:0098-4108
DOI:10.1080/15287399309531728
出版商:Taylor & Francis Group
年代:1993
数据来源: Taylor
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7. |
Effects on thyroid hormone metabolism and depletion of lung vitamin a in rats by airborne particulate matter |
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Journal of Toxicology and Environmental Health,
Volume 38,
Issue 4,
1993,
Page 419-434
G. A. H. Heussen,
G. J. Schefferlie,
M. J. G. Talsma,
H. van Til,
M. J. W. Dohmen,
A. Brouwer,
G. M. Alink,
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摘要:
Thyroxine (T4) and vitamin A are important regulators of normal epithelial differentiation and proliferation and might act in the promotion phase of carcinogenesis. Thyroid hormone and vitamin A metabolism are linked by a common plasma carrier protein, transthyretin (TTR). Polychlorinated biphenyls (PCBs) and related organochlorine compounds deplete vitamin A and thyroxine by interaction with TTR and altera1tion of their metabolism in hepatic and other organs. In the present report an outdoor airborne particulate matter (APM) extract was tested for both interaction with thyroid1 hormone and vitamin A metabolism, in order to address the question of whether APM has the potency to deplete vitamin A and thyroid hormones. Furthermore, studies were performed to characterize compounds present in APM that interact with TTR. A third aim was to compare the interaction of APM extracts with TTR and thyroxine‐binding globulin (TBG), the major carrier protein for thyroxine in humans. Results showed that a single treatment of rats with an outdoor APM extract depleted plasma thyroxine and triiodothyronine levels and increased plasma retinol levels gradually over the time period studied, while liver retinol, lung retinol, and retinyl palmitate levels were depleted by 30–50%. As outdoor APM was able to inhibit T4‐TTR binding in vitro, this suggests that the reduction in thyroxine levels in vivo is caused by the same phenomenon. Experiments showed that the neutral fraction of the APM extract accounted for most of the inhibitory activity on T4TTR binding. Polycyclic aromatic hydrocarbons and nitrated derivatives are not likely to be responsible for the activity of the neutral fraction, because several representatives of these compounds showed no or very little interaction with TTR. Pentachlorophenol, a compound with known inhibitory activity on T4TTR binding, was detected in the organic acid fraction of both a cigarette smoke sample and an outdoor APM sample. Finally, it was shown that several indoor and outdoor APM extracts only interact with TTR, but not with TBC. As APM has the potency to deplete lung vitamin A in vivo and vitamin A might have a protective effect in the process of lung carcinogenesis, APM might increase the susceptibility for the development of lung cancer.
ISSN:0098-4108
DOI:10.1080/15287399309531729
出版商:Taylor & Francis Group
年代:1993
数据来源: Taylor
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8. |
Airway inflammatory effect of hydrogen peroxide in guinea pigs |
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Journal of Toxicology and Environmental Health,
Volume 38,
Issue 4,
1993,
Page 435-448
Miwa Misawa,
Hiroyuki Arai,
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摘要:
Reactive oxygens are now considered to be important substances in promoting inflammatory process. Recently, airway inflammation has attracted attention closely linked to bronchial asthma. The present study was undertaken to examine whether hydrogen peroxide, one of the reactive oxygens, could produce airway inflammation. Airway inflammation was assessed by airway vascular permeability in terms of pontamine sky blue (PSB) exudation. Airway resistance was measured with a modified Konzett‐Rössler method and was expressed as a change in ventilation overflow. Inhalation of hydrogen peroxide (0.01–1.0 M) markedly caused a PSB exudation in a concentration‐dependent manner in all of the trachea, main bronchus, and lungs. The hydrogen peroxide‐induced PSB exudation effect was attenuated by pretreatment with catalase, although heat‐inactivated catalase had no inhibitory effect. Deferox‐amine, which inhibits conversion of hydrogen peroxide into hydroxyl radical, decreased the PSB exudation induced by hydrogen peroxide. On the other hand, inhalation of hydrogen peroxide (1.0 M) caused a significant and biphasic increase in ventilation overflow. This airway constriction was suppressed by pretreatment with inhaled catalase, but not by inhaled deferoxamine. These results indicate that hydrogen peroxide causes an intense airway inflammation; this inflammatory effect may be mediated not only by hydrogen peroxide itself but also by hydroxyl radical. Hydrogen peroxide and hydroxyl radical may thus play an important role in bronchial asthma and bronchitis through inducing airway inflammation.
ISSN:0098-4108
DOI:10.1080/15287399309531730
出版商:Taylor & Francis Group
年代:1993
数据来源: Taylor
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9. |
Editorial board |
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Journal of Toxicology and Environmental Health,
Volume 38,
Issue 4,
1993,
Page -
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ISSN:0098-4108
DOI:10.1080/15287399309531722
出版商:Taylor & Francis Group
年代:1993
数据来源: Taylor
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