Begell House Inc.
Journal of Environmental Pathology, Toxicology and Oncology
JEP(T)
0731-8898
23
4
2004
Erratum to Sulfur Free Radical Reactivity with Curcumin as Reference for Evaluating Antioxidant Properties of Medicinal Zingiberales, by Pukhrambam Chirangini, Gurumayum J. Sharma, & Swapan K. Sinha
2
10.1615/JEnvironPatholToxicolOncol.v23.i4.01
Modulation of c-Kit/SCF Pathway Leads to Alterations in Topoisomerase-I Activity in Small Cell Lung Cancer
16
10.1615/JEnvPathToxOncol.v23.i4.10
Gautam
Maulik
Lowe Center for Thoracic Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
Ajit
Bharti
Division of Medical Oncology and Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA
Ehsan
Khan
Division of Medical Oncology and Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA
Ryan J.
Broderick
Lowe Center for Thoracic Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
Takashi
Kijima
Lowe Center for Thoracic Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
Ravi
Salgia
Department of Medical Oncology and Therapeutics Research, Comprehensive Cancer Center, City of Hope National Medical Center, Duarte, CA 91010, USA
Small cell lung cancer (SCLC) is an aggressive type of lung cancer, for which cytotoxic chemotherapy appears to have reached its maximal efficacy. This neoplasm is characterized by the overexpression of several receptor tyrosine kinases (RTKs), especially c-Kit. The ligand for c-Kit is stem cell factor (SCF). In SCLC, SCF can influence c-Kit activation by autocrine or paracrine mechanisms. We have recently shown that the c-Kit/SCF pathway is operational in SCLC and can be inhibited by Glivec (STI571). Because the inhibition of topoisomerase-I (topo-I) is one approach used to treat SCLC, we determined the effects of c-Kit/SCF signaling on topo-I activity. A unique phosphorylation of c-Kit on amino acid 823 and amino acid 703 was identified with the SCF stimulation of H526 cells. We demonstrate that with SCF stimulation over 16 hours (dose response 0−100 ng/mL) in H526 SCLC cells (c-Kit positive, SCF responsive), a decrease in topo-I activity was observed, whereas in H82 SCLC cells (c-Kit negative, SCF unresponsive) there was no modulation of topo-I activity by SCF. Using STI571 (5 μ;M, 16 hours) to inhibit the c-Kit pathway following stimulation with SCF (100 ng/mL), an upregulation of topo-I activity was observed in H526 cells but not in H82 cells. Performing viability assays, we show that STI571 in combination with topo-I inhibition by camptothecin or SN38, the active metabolite of irinotecan, can cooperatively inhibit H526 cell viability (but not H82 cell viability) for 72 hours. We also show that STI571 does not directly inhibit topo-I activity in SCLC. The combination of STI571 with topo-I inhibition could provide a useful combination in the treatment of SCLC.
Effect of Platelet-Derived Growth Factor on the Development and Persistence of Asbestos-Induced Fibroproliferative Lung Disease
14
10.1615/JEnvPathToxOncol.v23.i4.20
Jian
Li
Section of Pulmonary Diseases, Critical Care and Environmental Medicine, Department of Medicine; and The Interdisciplinary Graduate Program in Molecular and Cellular Biology, Tulane University Health Sciences Center, New Orleans, Louisiana,USA
Halet G.
Poovey
Section of Pulmonary Diseases, Critical Care and Environmental Medicine, Department of Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana,USA
Juan Felipe
Rodriguez
Section of Pulmonary Diseases, Critical Care and Environmental Medicine, Department of Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana,USA
Arnold
Brody
Department of Pathology and Laboratory Medicine, Tulane University Medical Center 1430 Tulane Avenue New Orleans, LA 70112-2699, USA
Gary W.
Hoyle
Section of Pulmonary Diseases, Critical Care and Environmental Medicine, Department of Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana,USA
Platelet-derived growth factor (PDGF) isoforms and PDGF receptor-α are upregulated in fibroproliferative lesions in response to asbestos exposure. To examine the functional role of PDGF in asbestos-induced lung disease, we have evaluated the impact of PDGF-B overexpression in the lung on the development of pulmonary fibrosis induced by asbestos inhalation. Transgenic mice expressing PDGF-B from the surfactant protein C promoter and wild-type C57BL/6 mice were exposed to aerosolized chrysotile asbestos fibers via three different exposure regimens: 3 consecutive days to 9 mg/m3, once a week for 5 weeks to 12 mg/m3, or once a week for 8 weeks to 11 mg/m3. The 3-day exposure did not produce fibroproliferative lesions in SPC-PDGFB or wild-type mice, indicating that PDGF expression did not increase susceptibility to a subthreshold dose of asbestos. Transgenic and wild-type mice subjected to the 5-week exposure protocol exhibited similar fibrogenic lesions histologically 48 hours and 8 weeks postexposure, but lungs from transgenic mice had elevated lung hydroxyproline content 8 weeks postexposure relative to wild-type mice. In addition, SPC-PDGFB transgenic mice developed pronounced thickening of arterioles following the 5-week exposure regimen. Mice exposed to asbestos for 8 weeks and examined 10 months later showed pronounced, diffuse fibrotic lesions of terminal bronchioles and alveolar ducts, but no histological differences between transgenic and nontransgenic mice were observed. These results indicated that PDGF-B overexpression can stimulate increased collagen deposition and vascular smooth muscle hyper-plasia following asbestos inhalation and that a limited exposure (8 times) to chrysotile aerosol can produce long-lasting fibrotic lesions. The 8-week exposure regimen provides an animal model that encompasses an important aspect of human asbestosis—i.e., persistence of fibrosis for long periods after cessation of asbestos exposure.
Comparison of Genotoxicity of Textile Dyestuffs in Salmonella Mutagenicity Assay, In Vitro Micronucleus Assay, and Single Cell Gel/Comet Assay
12
10.1615/JEnvPathToxOncol.v23.i4.30
Klaus-M.
Wollin
Lower Saxony State Agency for Ecology, Hannover, Germany
Bernd-D.
Gorlitz
Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany
The mutagenicity of textile dyes is an important consideration for the assurance of consumer protection and work safety. The mutagenicity testing of textile dyestuffs is crucial for accurately predicting health risks for consumers and workers exposed to dyes. Unfortunately, these data are often lacking. We studied the genotoxic activity of ten selected commercial textile dyestuffs, which are made up of mixtures of azo dyes and azo metal complex dyes as well as two anthraquinone dyestuffs. We used the Salmonella mutagenicity assay and cultured human keratinocytes (HaCaT cell line). In the S. typhimurium strain TA98, with and without S9, eight often dyestuffs investigated, and in strain TA 100, with and without S9, six often dyes caused frameshift mutations and base-pair substitutions in the dose range of 1—5000 μ;g/plate in a dose-related manner. All dyes, including those negative in the Salmonella mutagenicity assay, induced clastogenic effects in the in vitro micronucleus (MN) test in HaCaT cells as direct-acting mutagens in the concentration range of 5—150 μ;g/mL and with maximum MN frequencies between 1.1 and 7.2%, compared to negative controls that showed 0.2—0.4% MN cells. In the single cell gel/comet assay, all ten dyestuffs investigated caused DNA damage in HaCaT keratinocytes. The alkaline (pH >13) version used is capable of detecting DNA single strand breaks, alkali-labile sites, and DNA—DNA/DNA—protein cross-linking. Under the conditions of these screening tests, the textile dyes investigated are direct-acting genotoxic substances. The HaCaT cells testing protocol proposed has been shown to be an appropriate test system for evaluating mutagenicity of textile dyes on a base level.
Genotoxicity of Degradation Products of Textile Dyes Evaluated with rec-Assay After PhotoFenton and Ligninase Treatment
8
10.1615/JEnvPathToxOncol.v23.i4.40
Ekta
Choudhary
Department of Microbiology, Panjab University, Chandigarh - 160 014, India
Neena
Capalash
Department of Biotechnology, Panjab University, Chandigarh, India
Prince
Sharma
Department of Microbiology, Panjab University, Chandigarh - 160 014, India
Fourteen textile and biological dyes, belonging to the azo, triphenylmethane, anthraquinone, heterocyclic, oxazine, and methine/polymethine groups, were degraded using the PhotoFenton treatment (PFT) and the Phanerochaete chrysosporium crude ligninase enzyme (ED) treatment. The genotoxicity of the dyes and of their degradation products were assessed with the rec-assay. We found that the genotoxicity depended on the dye and on the method of degradation. In general, PFT was better than ED in decreasing the genotoxicity. Basic dyes showed complete or maximum loss of genotoxicity, whereas the vat group was more resistant. The azo group showed varied results. Crystal Violet was the only dye whose genotoxicity increased after PFT. Our results suggest that PFT and ED are two effective treatment methods to reduce the genotoxicity of dyes in waste waters.
Protective Effect of Diphenylmethyl Selenocyanate Against Carbon Tetrachloride-Induced Hepatotoxicity In Vivo
10
10.1615/JEnvPathToxOncol.v23.i4.50
Rajat Kumar
Das
Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Kolkata, India
Sukta
Das
Department of Cancer Chemoprevention, Chittarajan National Cancer Institute, Kolkata, India
Sudin
Bhattacharya
Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Kolkata, India
Carbon tetrachloride (CCl4) is a known hepatotoxic compound working through the generation of reactive free radicals. Selenium (Se) is an essential trace element required by animals and humans for protection against xenobiotic compounds. In this study, Se, as diphenylmethyl selenocyanate, has been evaluated for its protective action against CCl4-induced hepatotoxicity in Swiss albino mice. Treatment with Se compound was found to upregulate different phase II detoxifying enzymes (catalase, superoxide dismutases, reduced glutathione, and glutathione transferase) in liver of mice challenged with different doses of CCl4 as compared to the CCl4 control, when measured after 24 hours of CCl4 treatment (p p < 0.01) inhibited the level of membrane lipid peroxidation and serum transferase activity (ALT and AST) in the treated group as compared to the control group.
Mutagenic Potential of Mancozeb in Salmonella typhimurium
6
10.1615/JEnvPathToxOncol.v23.i4.60
Yogeshwer
Shukla
Environmental Carcinogenesis Division, Industrial Toxicology Research Centre,Lucknow, India
Pankaj
Taneja
Environmental Carcinogenesis Division, Industrial Toxicology Research Centre, Lucknow, India
Annu
Arora
Environmental Carcinogenesis Division, Industrial Toxicology Research Centre,Lucknow, India
Neeraj
Sinha
Division of Toxicology, Central Drug Research Institute, Lucknow, India
Mancozeb, a dithiocarbamate fungicide, was examined for its possible mutagenic activity using Salmonella typhimurium tester strains TA97a, TA98, TA100, and TA102. We found that Mancozeb exhibited toxic effects at the dose of 40 μ;g/plate and higher with all tester strains. Mancozeb showed dose-dependent increases in the number of revertants with and without metabolic activation when it was dissolved in DMSO or acetone with strain TA97a; however, the number of revertants at the highest dose was less than two-fold compared to control values. We postulate that the true mutagenic potential of Mancozeb may be masked by its toxic effect to the tester strain used.
Urinary Excretion of Nickel After Dermal Application of Nigerian Light Crude Oil
4
10.1615/JEnvPathToxOncol.v23.i4.70
Ibiba F.
Oruambo
Department of Chemistry, Rivers State University of Science and Technology, Nkpolu, Port Harcourt, Rivers State, Nigeria
We examined the pattern of excretion of crude oil nickel (CON) in urine and feces. Adult male guinea pigs were treated with a single dose of 5mL/kg b.w. Nigerian Bonny light crude oil applied on the skin. Untreated guinea pigs served as controls. The CON content was measured spectrophotometrically by the dimethylglyoxime reaction following nitric acid:perchloric acid: sulfuric acid (3:1:1) digestion of blood, urine, and feces samples at 2, 4, 8, and 16 days after the crude oil application. We found a peak of CON excretion in the urine at 2 days and a return to the control level at 16 days. There was no change in the CON content in the feces during the observation time. We found a peak of CON content in the blood at 8 days and a return to control values at 16 days. The implication of these excretion and transport patterns of CON is discussed vis-a-vis the potential application of the urinary nickel content as a valid biochemical indicator of human exposure to environmentally spilled crude oil.
Volume 23 Indices
8
10.1615/JEnvironPatholToxicolOncol.v23.i4.90