Organic Lead Compounds Research Articles

Abstract 3910: Identification of lead organic compounds active against stem cell-like neuroblastoma cells by high throughput screening

Abstract Cancer stem cells (CSCs) are plastic in nature, a characteristic that hampers cancer therapeutics. We previously reported the establishment of induced neuroblastoma (NB) stem cells (iCSC), which were stable stem cell-like NB cells in sphere culture. These cells recapitulated the in vivo histological phenotypes of Large-Cell NB (LCN), the most aggressive and deadly subset of NB, including vesicular nuclei and two to three prominent nucleoli (PNAS Vol. 110: 6097-102 2013). In addition to the LCN phenotype, high-level expression MYC or MYCN is the consistent feature of the iCSC xenografts grown in immune-compromised mice. The goal of this study is to identify lead organic compounds active against NB iCSCs by high throughput screening. By using MTS assays, the SKNAS iCSC and the parental monolayer cells were used to screen the Prestwick Chemical Library®, containing 1200 FDA-approved small molecules. Growth suppressive compounds were defined as they exhibited cell survival reduction of greater than 80% compared to DMSO control. There were unexplored compounds with significant antineoplastic activity among existing antibacterial, antifungal, antiprotozoal, and anthelmintic compounds. Among the compounds screened, we identified a dozen of small molecules that were preferentially growth suppressive to the SKNAS iCSC over the monolayer cells. The secondary MTS assay confirmed so far that Chlorhexidine (antiseptic), Benzethonium (antiseptic) and Digoxin (cardiac glycoside) were potential anti-NB iCSC agents: they were more effective in suppressing growth of the SKNAS iCSC than the monolayer cells. In addition, these compounds exhibited MYC destabilizing activity in the SKNAS iCSC. Notably, JQ1, the recently identified MYC destabilizer, was less effective than Chlorhexidine, Benzethonium and Digoxin in suppressing growth of SKNAS iCSC. The above three compounds also showed the MYCN destabilizing effect in another pair of MYCN-amplified SKNBE(2)C iCSCs and SKNBE(2)C monolayer cells. We are currently completing characterization of the small molecules identified with focus on their anti- iCSC growth and anti-MYC/MYCN effects. This study would reveal specific pathways that regulate biological activities of the CSCs. In addition, it is a promising approach that could lead to development of safe and effective anti-cancer therapeutics not only for NB but also other cancer types. Citation Format: Naohiko Ikegaki, Kiira Ratia, Ruth Hsiao, Mariko M. Limpar, Sarah Lomahan, Xao X. Tang. Identification of lead organic compounds active against stem cell-like neuroblastoma cells by high throughput screening. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3910. doi:10.1158/1538-7445.AM2014-3910

268 The mortality experience of UK workers occupationally exposed to lead

ObjectivesAlthough the worldwide occurrence of lead in the environment has decreased greatly due to the elimination of most leaded petroleum, occupational exposures continue primarily via the lead battery industry and...

Origin of damp-heat induced cell degradation

The degradation of the edge regions of crystalline silicon cells after damp-heat tests is a common phenomenon which can be observed in the electroluminescence images of most c-Si PV modules after damp-heat aging. However, the origin of this damp-heat induced degradation effect is unknown. Therefore, we investigated the degradation behavior of laminates with different designs, including laminate types with an open, thus breathable, front-side and two standard designs with one or two layers of EVA in front of the cell, respectively. This way, the influence of permeation properties and possible barrier effects on the degradation of the cell were investigated. The laminates were subjected to damp-heat aging tests at 80% r.h., 80°C and 90°C, respectively, for up to 2500h. Electroluminescence imaging showed degradation after 2000h of damp-heat aging at 90°C for the standard laminate designs. No cell degradation was found for the breathable laminates. Measurements of the internal quantum efficiency (IQE) did not reveal a change of the recombination rate, thus the corrosion of the grid is the most likely cause of the degradation. This hypothesis was confirmed by an increased series resistance in the degraded areas. In those areas, aggregates of small needles were observed which could be identified as organic lead compounds by EDX. Since no hints of degradation could be found for the breathable laminates, an impact of the acetic acid as one corrosive degradation product from the encapsulant on the metal corrosion is very likely.

Chromosomal Study on Lead Exposed Population

Exposure to extremely toxic substance like lead might lead to a broad range of undesirable health consequences. As a result of lead poisoning both adults and children experience adverse physical conditions. The objective of the present study is to estimate the level of lead in the blood of the exposed population and analyze the haematological parameters along with chromosomal damage. Lead level from blood was estimated by atomic absorption spectrophotometry. Microcytic anaemia was present in the individuals with high lead level in the blood. Leucocyte culture revealed higher percentage of chromosomal aberrations in the individuals with high lead content in the blood. Further studies will help to define the role of genes in lead intoxication to prevent irreversible damage. Present Address: Dr. Urmisha Das. Research & Publication Executive Lincoln University College Malaysia Address for correspondence: Dr. Urmisha Das. 17/25 Shambhunath Das Lane, Kolkata 700 050, West Bengal, India Telephone: +91 9830228782 E-mail: urmishadas@gmail.com INTRODUCTION During past decades, due to rapid industrialization, the evaluation of potential toxic effect of industrial emissions on residential populations has assumed considerable importance. India is a multiracial population with a wide variety of life styles and microclimates. The effect of various heavy metals on the human population is a widely discussed topic. Lead is a heavy metal, which has many adverse effects on human physiology. Lead is everywhere in the environment as a result of natural occurrence and its industrial use. The primary sources of environmental exposure to lead are paint and drinking water. Most of the overt toxicity from lead results from environmental and industrial exposure (Dregus and Klaassen 2001). Elevated levels of lead in the air are associated with elevated blood lead level in humans (Thomas et al. 1999). Lead is found in storage batteries, lead solders, pipes, construction materials, dyes and wood preservatives (Farjami et al. 2004). Lead is also present in paint, leaded gasoline, cable sheathing and many building materials. It may also be found at firing ranges (from bullet dust) (UNICEF 2000) and in some contaminated herbal remedies and candies (Hu 2005). Though organic lead compounds (tetraethyl lead) have been used as gasoline additives; inorganic lead compounds are the species of current concern. Lead is ubiquitous in the environment and is a major environmental pollutant of air, water and soil. Lead toxicity depends on the site of entry of lead into the body (ingested or absorbed through skin), nature of lead (organic or inorganic), period of exposure, age and sex of the individual and the socio-economic condition. The occurrence of lead poisoning depends on the developmental stage, behavior, nutritional status, and metabolism of an exposed individual. Generally, males have higher blood lead levels than females, even when the exposures to both groups are controlled (Walter et al. 1980). The objective of the present study is to observe the effect of lead on the haematopoietic

Organic Lead Toxicology

Lead is one of the oldest known and most widely studied occupational and environmental poison. Despite intensive study, there is still debate about the toxic effects of lead, both from low-level exposure in the general population owing to environmental pollution and historic use of lead in paint and plumbing and from exposure in the occupational setting. Significant position have organic lead compounds used more than 60 years as antiknock additives in gasoline. Chemical and toxicological characteristics of main tetraalkyl leads used as gasoline additives are discussed in this article. The majority of industries historically associated with high lead exposure have made dramatic advances in their control of occupational exposure. However, cases of unacceptably high exposure and even of frank lead poisoning are still seen, predominantly in the demolition and tank cleaning industries. Nevertheless, in most industries blood lead levels have declined below levels at which signs or symptoms are seen and the current focus of attention is on the subclinical effects of exposure. The significance of some of these effects for the overt health of the workers is often the subject of debate. Inevitably there is pressure to reduce lead exposure in the general population and in working environments, because current studies show that no level of lead exposure appears to be a 'safe' and even the current 'low' levels of exposure, especially in children, are associated with neurodevelopmental deficits.

Toxicité du plomb et de ses dérivés

The mining of lead-containing ores began in antiquity; this metal has more uses than any other one. The toxic effects of lead have also been described very early in history, and lead poisoning remains a problem in most countries: occupational exposure is frequent; children poisoning from paint chips or dust is pandemic in some developed countries including France and the USA; in areas where poorly mineralised drinking-water is distributed, lead can leach from water pipes and solder… This paper describes the poisonings due to inorganic and organic lead compounds: mains sources of these substances and circumstances of poisoning, toxicokinetics and toxic effects of lead including carcinogenicity, reproductive and developmental effects, organisation of the screening, diagnosis and medical management of lead poisoning in young children, and the principles of medical surveillance of occupational lead exposure.

Synthetic Applications of Organic Germanium, Tin and Lead Compounds (Excluding R3MH)

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Similarities and Differences of Organic Compounds of Germanium, Tin and Lead

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Recent Advances in Structural Chemistry of Organic Germanium, Tin and Lead Compounds

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Theoretical Studies of Organic Germanium, Tin and Lead Compounds

AbstractFor Abstract see ChemInform Abstract in Full Text.

Capillary-channeled polymer fibers as stationary phases in liquid chromatography separations

A method utilizing capillary-channeled polymer (C-CP) fibers as stationary phases in high-performance liquid chromatographic separations has been investigated. Polymeric fibers of differing backbones (polypropylene and polyester) having nominal diameters of ∼50 and ∼35 μm and a channeled structure on their periphery were packed into stainless steel tubing (305×4.6 mm I.D.) for use in reversed-phase separations of various mixtures. The fibers have eight channels running continuously along the axis which exhibit very high surface activity. As such, solvent transport is affected through the channels through wicking action. Bundles of 1000–3000 fibers are loaded co-linearly into the tubing, providing flow channels extending the entire length of the columns. As a result, backing pressures are significantly lowered (∼50% reduction) in comparison to packed-sphere columns. In addition, the capital costs of the fiber material (<US$0.25 per column) are very attractive. Flow-rates of up to 5 ml/min can be used to achieve near baseline separation of related compounds in reasonable run times, indicating very fast mobile phase mass transfer (C-terms). The polymer stationary phases demonstrate high selectivity for a wide variety of analytes with gradient elution employed successfully in many instances. Specifically, separations of three polyaromatic hydrocarbons (benzo[ a]pyrene, chrysene, pyrene), mixtures of both organic and inorganic lead compounds [chlorotriethyllead, chlorotriphenyllead, lead nitrate, lead(II) phthalocyanine], and a lipid standard of triglycerides were accomplished on the polymeric stationary phases. Other species of biological interest, including groups of aliphatic and aromatic amino acids have also been effectively separated. The reversed-phase nature of the fiber surfaces is supported through atomic force microscopy measurements using hydrophilic and hydrophobic functionalized polystyrene beads as the probe tips. Separations of the various analytes demonstrate the feasibility of utilizing C-CP fibers as stationary phases in reversed-phase LC. It is envisioned that columns of this nature would be particularly useful in prep-scale separations as well as for immobilization matrices for organic constituents in aqueous environments.

Evaluation of the initial weathering rate of Istria stone exposed to rain action, in Venice, with X-ray photoelectron spectroscopy

Samples of Istria stone were exposed in rain-washed conditions for 6 and 18 months, in the industrial and marine environment of Venice. To assess the initial stages of weathering, the exposed samples were analyzed by using X-ray photoelectron spectroscopy (XPS) and other analytical techniques, such as Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy coupled with energy dispersive X-ray analysis (SEM–EDS). Within a 6-month period, XPS revealed the deposition of sulfates, calcium silicates, carbonaceous particles, nitrogen compounds and organic compounds of lead, fluorine and chlorine. After an 18-month exposure period, the exposed surface exhibited pollutant compounds of sulfates, fluorine and nitrogen along with new-formed pollutant compounds of phosphorus and zinc. The appearance of silicon, aluminum and iron compounds indicates either dissolution of the argillaceous inclusions of the carbonate matrix or deposition of air-borne particles. The other applied analytical techniques evidence alteration features related more to morphological modification and less to chemical changes. Therefore, XPS revealing deposition of typical components of atmospheric pollution, as well as either deposition or dissolution of soil-derived and intrinsic elements evidences the initial weathering rate of exposed Istria stone to rain action.

Influence of amphiphilic compounds on membranes.

On the basis of Gortel & Grendel (J. Exp. Med., 1925, 41, 439-494) discovery, the importance of the lipid bilayer as an integral and indispensible component of the cell membrane is discussed. In particular, attention focuses on the interaction between membranes and amphiphilic substances. The effect on membranes of quaternary ammonium salts, both in the form of pesticides and oxidants as well as organic compounds of tin and lead are discussed in greater detail.

Preface

The field of natural products is inevitably closely associated with organic chemistry: living organisms provide an extremely wide diversity of organic molecules. This is the first issue on "Natural Product Chemistry" in the journal "Current Organic Chemistry" and it is designed to focus on compounds in Nature which exhibit interesting biological activities. The aim is to provide an update on results in different fields of research and also to present recent advances in methodology and in the introduction of new areas of investigation. Six different chapters have been included in this issue, covering bioactive organic compounds from several different sources: from plants, fungi, marine algae and, to a lesser extent, microorganisms. Arnold Vlietinck and Dirk Vanden Berghe review the latest results concerning antiviral compounds from plants, while Lars Bohlin gives a summary of new plant-derived antiinflammatory molecules, with emphasis on platelet activating factor (PAF) antagonistic activity. In an attempt to cover an area of great potential interest which is only sparingly reported in the scientific literature, the subject of nematicidal compounds from higher fungi has been tackled by Heidrun Anke and Olov Sterner, specialists in the study of mushrooms. Marine algae are a category of organisms from the sea which are the source of many intriguing organic molecules and possible new lead compounds. Corrado Tringali has provided an insight into some of the diverse stn.Jctures which have been discovered and the associated biological activities. An important phenomenon when considering the bioactivities of natural products is the influence of light. Until recently, very few people have taken into account the fact that the presence or absence of light can have dramatic consequences on the magnitude of the activities: in certain cases, a natural product may be completely inactive in the dark. Neil Towers has devoted a large amount of research effort to this particular field and in chapter 4, he gives a lucid account of the results observed. Finally, Olivier Potterat reviews antioxidants and free radical scavengers of natural origin. Free radicals are implicated in many different physiological processes, such as aging, cancer, coronary heart disease and inflammation-related complications. For this reason, the discovery of agents which inhibit oxidative damage can lead to the development of products with important repercussions on human health. Many resources are currently being expended in this aspect of disease prevention. The contributors are all authorities in their particular fields and it is hoped that the readers will have the opportunity of keeping abreast of the most recent developments in the areas selected. Future dedicated issues of "Current Organic Chemistry" will treat other natural product subject matter in a similar fashion.

Erythrocyte Hemolysis by Organic Tin and Lead Compounds

The effect of trialkyllead and trialkyltin on pig erythrocyte hemolysis has been studied and compared. The results of experiments showed that the hemolytic activity of organoleads increases with their hydrophobicity and follows the sequence: triethyllead chloride < tri-n-propyllead chloride < tributyllead chloride. And similarly in the case of organotins: triethyltin chloride < tri-n-propyltin chloride < tributyltin chloride. Comparison of the hemolytic activity of organoleads and organotins indicates that the lead compounds exhibit higher hemolytic activity. The methods of quantum chemistry allowed to determine the maximum electric potential of the ions R3Pb+ and R3Sn+, and suggest a relationship between the potential and toxicity.

Case-control study of cancer risk in tetraethyl lead manufacturing.

A case-control study was conducted to investigate the relative risk of cancer detection among Du Pont employees who worked in a tetraethyl lead (TEL) manufacturing area. The study's objective was to determine whether the employees' risk of developing or dying from cancer was associated with occupational exposure to TEL. All malignant neoplasms detected in the active and pensioned employee population during the period 1956-1987 were studied. TEL exposure was estimated by the following measures: ever employed in the TEL area, years of employment in TEL, TEL exposure rank, and the TEL cumulative exposure index. TEL manufacturing exposed employees to both organic and inorganic lead compounds. Because the underlying data did not permit the exposure assessment to distinguish between organic and inorganic lead, the TEL exposure measures reflect exposure to the TEL manufacturing process itself. The effects of latency, cigarette smoking habits, and exposures to other known or suspected carcinogens at the plant were also assessed. A strong association was observed between exposure to the TEL manufacturing process and rectal cancer (the odds ratio was 3.7 with 90% confidence limits of 1.3-10.2 for the analysis of ever/never exposed to TEL). An exposure-response relationship was noted with a fourfold elevation in the odds ratio at the high-very high cumulative exposure level. These patterns were even more pronounced after assuming a 10 year latency. Similar results were obtained for cancers of the sigmoid colon. These findings suggest that exposure to the TEL manufacturing process may have played a causal role in the colorectal cancer experience at the plant. This position is supported by the graded exposure-response relationships, the consistency of the results across exposure measures, the specificity of the health outcome (i.e., colorectal cancer), and the strength of the association. However, the evidence for causality is not compelling. This is the first report of an association between TEL manufacturing and colorectal cancer, and the evidence is compatible with a wide range of causal (i.e., indirect vs. direct acting; initiating vs. promoting) and noncausal (i.e., statistical and methodological bias; coincidence) interpretations.

The Chemistry of Organic Germanium, Tin and Lead Compounds Edited by Saul Patai (The Hebrew University). Wiley: New York. 1995. xv + 997 pp. $625. ISBN 0-471-94207-3.

ADVERTISEMENT RETURN TO ISSUEPREVBook ReviewNEXTThe Chemistry of Organic Germanium, Tin and Lead Compounds Edited by Saul Patai (The Hebrew University). Wiley: New York. 1995. xv + 997 pp. $625. ISBN 0-471-94207-3.Peter GasparView Author Information Washington UniversityCite this: J. Am. Chem. Soc. 1996, 118, 41, 10010Publication Date (Web):October 16, 1996Publication History Published online16 October 1996Published inissue 1 January 1996https://doi.org/10.1021/ja9553718Copyright © 1996 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views127Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (21 KB) Get e-AlertsSUBJECTS:Germanium,Materials,Organic compounds,Photochemical synthesis,Photoelectron spectroscopy Get e-Alerts

Exposure of the deck crew to carcinogenic agents on oil product tankers

Work on deck on eight oil product tankers was examined. The purpose was to evaluate the need for improvement of the working environment to reduce the risk of occupational cancer. Benzene, polyaromatic hydrocarbons (PAHs) and organic lead compounds were sampled, and the crew answered a questionnaire on acute health effects. By area monitoring, benzene was generally found to be in the range from the detection limit, of 0.01 ppm, up to 1.15 ppm, but one tanker which loaded gasoline with the hatches open had levels up to 55 ppm. Personal monitoring showed exposure levels in the range 0.01–1.15 ppm. The PAH-levels and the levels of organic lead were low. No seamen were observed using respiratory protective equipment. Central nervous system symptoms were reported by the crew with the highest exposures to benzene although benzene may not be the only cause. The exposure to benzene and other hydrocarbons on the deck of oil product tankers ought to be reduced.

ChemInform Abstract: Recent Advances in the Chemistry of Bivalent Organic Compounds of Germanium, Tin and Lead

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Effects of organometals on cellular signaling. I. Influence of metabolic inhibitors on metal-induced arachidonic acid liberation.

Organic lead and tin compounds stimulate an increase of free arachidonic acid (AA) in HL-60 cells. This fatty acid is involved in numerous health problems and physiological mechanisms. Three major pathways result in a liberation of AA from membrane phospholipids and there is evidence that G-proteins serve as couplers within all three pathways. Therefore we investigated the influence of pertussis toxin (PT) on the organometallic-induced AA liberation. The effect of all studied compounds (organotin and organo-lead) was diminished by PT. We conclude that the organometals activate PLA2 to some extent via a PT-sensitive pathway. The ionophor A 23187 (1-10 microM) led to an increase of free AA by raising the intracellular Ca2+ level. One of the postulated ways of AA release is via Ca2+ channel activation; phospholipases are Ca2+ dependent. Thus, we examined the necessity of free intracellular Ca2+ for the organometallic effect. The Ca2+ chelator EGTA inhibited the increase of free AA induced by organometals. This is true also for verapamil, a Ca2+ channel blocker. Quinacrine, which is thought to be an inhibitor of phospholipase A2 (PLA2), prevented the AA liberation from membrane phospholipids induced by organometals. This could be due to the inhibition of PLA2, but it could also be the result of an inhibited Ca2+ influx.