Begell House Inc.
Journal of Environmental Pathology, Toxicology and Oncology
JEP(T)
0731-8898
28
3
2009
Occupational Toxicology of Nickel and Nickel Compounds
177-208
10.1615/JEnvironPatholToxicolOncol.v28.i3.10
Jinshun
Zhao
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505
Xianglin
Shi
Division of Nutritional Sciences, Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY, USA; Center for Research on Environmental Disease, College of Medicine, University of Kentucky,
Lexington, KY, USA; Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY, USA
Vincent
Castranova
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505
Min
Ding
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505
nickel
nickel compounds
occupational exposure
toxicology
occupational exposure limits
toxicokinetics
biological monitoring
acute toxicity
chronic toxicity
genotoxicity
reproductive toxicity
carcinogenicity
molecular mechanisms of carcinogenesis
Nickel and nickel compounds are widely used in industry. The high consumption of nickel products inevitably leads to occupational and environmental pollution. In occupational settings, exposure to nickel and nickel compounds occurs primarily during nickel refining, electroplating, and welding. The most common airborne exposures to nickel in the workplace are to insoluble nickel species, such as metallic nickel, nickel sulfide, and nickel oxides from dusts and fumes. The chemical and physical properties of nickel and nickel compounds strongly influence their bioavailability and toxicity. The lung and the skin are the principal target organs upon occupational exposure. inhalation exposure is a primary route for nickel-induced toxicity in the workplace. The most important adverse health effects due to occupational exposure to nickel and its compounds are skin allergies, lung fibrosis, and lung cancer. The exact mechanisms of nickel-induced carcinogenesis are not clear. This review summarizes the current knowledge on occupational toxicology of nickel and its compounds. The subtopics include: chemical and physical properties, uses, occupational exposures, occupational exposure limits, toxicokinetics, biological monitoring, acute toxicity, chronic toxicity, genotoxicity, reproductive toxicity, carcinogenicity, molecular mechanisms of carcinogenesis, and gaps in knowledge.
Regulation of Heme Synthesis and Proteasomal Activity by Copper: Possible Implications for Wilson's Disease
209-221
10.1615/JEnvironPatholToxicolOncol.v28.i3.20
Ravit
Hait-Darshan
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel
Tania
Babushkin
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel
Zvi
Malik
The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Israel
ALAD
ATP7B
PBGD
proteasome
protoporphyrin IX
ubiquitin
Wilson's disease (Wd) is a genetic disorder resulting in Cu2+ accumulation, and is caused by mutations in the ATP7B gene, the copper transporter. In vivo studies show a correlation between Cu2+ accumulation and malfunction of the heme biosynthesis pathway. In this study, we describe multiple effects of Cu2+ accumulation on heme synthesis, which, in turn, affect proteasomal activity. Cu2+ toxicity was examined in two hepatocellular carcinoma cell lines, HepG2 and Hep3B, with Hep3B cells containing an integrated hepatitis B virus genome. Exposure of HepG2 and Hep3B cells to Cu2+ inhibited the enzymes PBGD and ALAD of the heme synthesis pathway and, in parallel, upregulated heme oxygenase-1 (HO-1). Proto-porphyrin IX (PpIX) and the heme pool were reduced as a result of these processes. PpIX synthesis was found to be lower in cells expressing the mutant ATP7B (P1134P), compared to those expressing the WT enzyme. Proteasomal activity was inhibited under Cu2+ treatment in HepG2 cells; however, Cu2+ induced marked proteosomal acceleration in Hep3B cells. Under these conditions, Ub-conjugated proteins were gradually accumulated, whereas treatment with bathocuproine disulfonic acid (BCS), a Cu2+ chelator, reversed this effect. In conclusion, our data suggest that copper downregulates the heme synthesis pathway in hepatocellular cells and further reduces it in the presence of mutated ATP7B.
Effects of Shear Stress on Intracellular Calcium Change and Histamine Release in Rat Basophilic Leukemia (RBL-2H3) Cells
223-230
10.1615/JEnvironPatholToxicolOncol.v28.i3.30
Wenzhong
Yang
Surface Physics Laboratory (National Key Laboratory), Department of Physics, Fudan University, Shanghai, China
Ji-Yao
Chen
Surface Physics Laboratory (National Key Laboratory), Department of Physics, Fudan University, Shanghai, China
Luwei
Zhou
Surface Physics Laboratory (National Key Laboratory), Department of Physics, Fudan University, Shanghai, China
massage
shear stress
mast cell
intracellular calcium
histamine
TRPV4
Massage, one form of physical therapy, is widely used for a large number of musculoskeletal disorders, but its exact mechanism still remains to be elucidated. One hypothesis is that the shear stress caused by massage may induce cutaneous mast cells to release histamine, thereby improving the local tissue microcirculation of blood. In the present work, a mast cell line (rat basophilic leukemia cells, RBL-2H3) was used in vitro to study cellular responses to the stimulus of shear stress generated by a rotating rotor in a cell dish. The intracellular calcium ([Ca2+]c) was studied by confocal fluorescence microscopy with Fluo-3/AM staining and the released histamine was measured with a fluorescence spectrometer using o-phthalaldehyde (OPA) staining. An elevation of [Ca2+]c occurred immediately after the shear stress, followed by histamine release. However, both [Ca2+]c increase and histamine release disappeared when a Ca2+-free saline was used, indicating that the rise in the [Ca2+]c is due to a Ca2+ influx from the extracellular buffer. Furthermore, Ruthenium red, a transient receptor potential vanilloid (TRPV) inhibitor, could effectively block the shear stress—induced histamine release, suggesting that TRPV membrane proteins are the likely targets of the shear stress. Because histamine is a well-known mediator of microvascular tissue dilation, these results may have an important impact on understanding the mechanism involved in massage therapy.
2Am-DNT Induces Cell Death and Apoptosis in Human Cells
231-234
10.1615/JEnvironPatholToxicolOncol.v28.i3.40
Hirendranath
Banerjee
Department of Biological and Pharmaceutical Sciences, Elizabeth City State University, University of North Carolina, USA
Z.
Hawkins
Departments of Biological Sciences and Pharmaceutical Science, Elizabeth City State University, Elizabeth City, NC 27909, USA
M.
Yakubu
Departments of Biological Sciences and Pharmaceutical Science, Elizabeth City State University, Elizabeth City, NC 27909, USA
D.
Smoot
Departments of Biological Sciences and Pharmaceutical Science, Elizabeth City State University, Elizabeth City, NC 27909, USA
M.
Asktorab
Department of Medicine, Howard University Cancer Center, Washington, DC 20059, USA
S. K.
Dutta
Department of Medicine, Howard University Cancer Center, Washington, DC 20059, USA
apoptosis
breast cancer cells
cytotoxicity
During microbial or mammalian cell metabolism, TNT (2,4,6-tinitrotoluene) is reduced to 2Am-DNT (2-amino-4,6-dinitrotoluene), 4Am-DNT, or 2,4-diamino-NT (2,4-diaminonitrotoluelne) depending on the specific organism. The metabolite 2Am-DNT is the most common of the TBT biotransformation pathways in bacterial and fungal species studied to date. in the mammalian liver cells, TNT is metabolized to 2Am-DNT by the P450 enzyme system. Apoptosis is rapidly emerging as a relevant endpoint for detecting low-dose toxin exposure. We report in this study that 2Am-DNT treatment of mammalian cells causes cell death by apoptosis. Cell death was assayed by the Trypan Blue method. Apoptotic changes, such as DNA break down, were detected in treated cells by the production of a dark-brown DAB (diaminobenzidine) signal using the Fragel™ Klenow DNA fragment detection system, by immunohistochemical techniques with fluorescence microscopy, and by using a microplate reader for a single-stranded DNA binding assay. All of these results showed that 2am-DNT is toxic to mammalian cells and induces apoptosis.
Modern Concepts of the Diagnosis and Treatment of Psoriasis
235-240
10.1615/JEnvironPatholToxicolOncol.v28.i3.50
Richard
Edlich
Legacy Verified Level I Shock Trauma Center Pediatrics and Adults, Legacy Emanual Hospital; and Plastic Surgery, Biomedical Engineering and Emergency Medicine, University of Virginia Health System, USA
Allyson L.
Fisher
Legacy Emanuel Hospital, Portland, OR, USA
Margot E.
Chase
Legacy Emanuel Hospital, Portland, OR, USA
Carroll M.
Brock
Legacy Emanuel Hospital, Portland, OR, USA
K. Dean
Gubler
Surgical Critical Care, Legacy Verified Level I Shock Trauma Center for Pediatrics and Adults, Legacy Emanuel Hospital, Portland, OR, USA
William B.
Long III
Trauma Specialists LLP, Legacy Verified Level I Shock Trauma Center for Pediatrics and Adults, Legacy Emmanuel Hospital, Portland, OR, USA
psoriasis vulgaris
pustular psoriasis
erythrodermic psoriasis
Psoriasis is a papulosquamous skin disease that is recognized as one of the most common immune-mediated disorders. At least nine chromosomal psoriasis susceptibility loci have been identified. It is important to emphasize that management of psoriasis begins with identification of the extent of the cutaneous disease. There are three clinical forms of psoriasis, to include psoriasis vulgaris, pustular psoriasis, and erythrodermic psoriasis. Treatments currently available are topical agents used predominantly for mild disease and for recalcitrant lesions in more severe disease, phototherapy for moderate disease, and systemic agents, including photochemotherapy, oral agents, and newer injectable biological agents, which have revolutionized the management of severe psoriasis.
Evaluation of Adverse Cardiac Effects Induced by Arsenic Trioxide, a Potent Anti-APL Drug
241-252
10.1615/JEnvironPatholToxicolOncol.v28.i3.60
K. G.
Raghu
Pharmacology Division,Central Drug Research Institute, Lucknow,UP; Biochemistry and Cell Culture Laboratory,Agroprocessing&Natural Products Division,National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram,Kerala,India
Govind Kumar
Yadav
Pharmacology Division, Central Drug Research Institute (CDRI), Lucknow, Uttar Pradesh (UP), India, 226001
Richa
Singh
Pharmacology Division, Central Drug Research Institute (CDRI), Lucknow, Uttar Pradesh (UP), India, 226001
A.
Prathapan
Biochemistry and Cell Culture Laboratory, Agroprocessing & Natural Products Division, National Institute for Interdisciplinary Science and Technology (NIIST), Thiruvananthapuram, Kerala, India, 695019
Sharad
Sharma
Toxicology Division, Central Drug Research Institute (CDRI), Lucknow, Uttar Pradesh (UP), India, 226001
Smrati
Bhadauria
Toxicology Division, Central Drug Research Institute (CDRI), Lucknow, Uttar Pradesh (UP), India, 226001
arsenic trioxide
action potential
ion channel modulators
GSH
antioxidant enzymes
histopathology
Arsenic trioxide (ATO/As2O3) is a promising drug for patients with a relapse of acute promyelocytic leukemia (APL); however, it frequently causes fatal arrhythmias. This study aims to investigate the various cellular and molecular mechanisms of adverse cardiac effects and the electrophysi-ological alterations caused by As2O3. We show the dose-dependent effect of ATO (0.2, 0.4, 0.8, 1.6, 3.2, 6.4 μ;m) on electrically driven cardiac action potential from the papillary muscle of the guinea pig. ATO causes a significant prolongation of action potential duration (APD) at various levels of repolarization, conduction delay, and increased triangulation, which is a novel marker for the proarrhythmic potential of a compound. Electrolyte imbalance (hypomagnesemia and hypokalemia) has also been found to cause amplification of ATO toxicity. Since ion channels play a very important role in the generation of cardiac action potential, we used various ion channel modulators such as choline, minoxidil, nifedipine, and verapamil to determine whether these agents could antagonize electrophysiological alterations caused by ATO. In in vivo experiments, ATO administration to animals for 10 days caused myocardial disorganization, interstitial edema and infiltration of inflammatory cells in the heart. Efforts were also made to screen the efficacy of vitamin C against ATO toxicity. ATO also caused a significant increase in the activity of certain clinically relevant enzymes for cardiac function and antioxidant mechanisms—such as serum creatine kinase isoenzyme, lactate dehydrogenase, glutathione peroxidase and reduced glutathione. In conclusion, ATO causes significant adverse cardiac effects and we suggest that cardiac function to be monitored during treatment with ATO. Our results also indicate that the status of the body's main electrolyte content (such as magnesium and potassium) is also an influencing factor on the magnitude of toxicity of arsenic trioxide.
Effect of Indoor Air Pollution from Biomass Fuel Use on Argyrophilic Nuclear Organizer Regions in Buccal Epithelial Cells
253-259
10.1615/JEnvironPatholToxicolOncol.v28.i3.70
Nandan Kumar
Mondal
Artificial Organs Laboratory, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland; Department of Experimental Hematology, Chittaranjan National Cancer Institute, Kolkata, India; Department of Zoology, Kabi Nazrul College
Anindita
Dutta
Department of Experimental Hematology, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata 700 026, India
Anirban
Banerjee
Department of Experimental Hematology, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata 700 026, India
Sreeparna
Chakraborty
Department of Experimental Hematology, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata 700 026, India
Twisha
Lahiri
Department of Experimental Hematology, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata 700 026, India
Manas Ranjan
Ray
Department of Experimental Hematology, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata 700 026, India
AgNOR
oral mucosa
biomass fuel
India
This study investigated the effect of indoor air pollution from biomass-fuel use on the expression of argyrophilic nucleolar organizer regions (AgNORs), an indicator of ribosome biosynthesis, in epithelial cells of oral mucosa. AgNORs were evaluated using cytochemical staining in 62 nonsmoking indian women (median age, 34 years), who cooked exclusively with biomass, and 55 age-matched women, who were from a similar neighborhood and cooked with relatively clean liquefied petroleum gas (LPG). Concentrations of particulate pollutants in indoor air were measured using a real-time aerosol monitor. Compared to the LPG-using controls, biomass-fuel users showed a remarkably increased number of AgNOR dots per nucleus (6.08 ± 2.26 vs 3.16 ± 0.86, p < 0.001), AgNOR size (0.85 ± 0.19 vs 0.53 ± 0.15 μ;m2, p < 0.001), and percentage of AgNOR-occupied nuclear area (4.88 ± 1.49 vs 1.75 ± 0.13%, p < 0.001). Biomass-using households had 2 to 4 times more particulate pollutants than that of LPG-using households. The changes in AgNOR expression were positively associated with PM10 and PM2.5 levels in indoor air after controlling for potential confounders such as age, kitchen location, and family income. Thus, biomass smoke appears to be a risk factor for abnormal cell growth via upregulation of ribosome biogenesis.