Jong-Il Weon

Toxicogenomic approaches for understanding molecular mechanisms of heavy metal mutagenicity and carcinogenicity

Heavy metals that are harmful to humans include arsenic, cadmium, chromium, lead, mercury, and nickel. Some metals or their related compounds may even cause cancer. However, the mechanism underlying heavy metal-induced cancer remains unclear. Increasing data show a link between heavy metal exposure and aberrant changes in both genetic and epigenetic factors via non-targeted multiple toxicogenomic technologies of the transcriptome, proteome, metabolome, and epigenome. These modifications due to heavy metal exposure might provide a better understanding of environmental disorders. Such informative changes following heavy metal exposure might also be useful for screening of biomarker-monitored exposure to environmental pollutants and/or predicting the risk of disease. We summarize advances in high-throughput toxicogenomic-based technologies and studies related to exposure to individual heavy metal and/or mixtures and propose the underlying mechanism of action and toxicant signatures. Integrative multi-level expression analysis of the toxicity of heavy metals via system toxicology-based methodologies combined with statistical and computational tools might clarify the biological pathways involved in carcinogenic processes. Although standard in vitro and in vivo endpoint testing of mutagenicity and carcinogenicity are considered a complementary approach linked to disease, we also suggest that further evaluation of prominent biomarkers reflecting effects, responses, and disease susceptibility might be diagnostic. Furthermore, we discuss challenges in toxicogenomic applications for toxicological studies of metal mixtures and epidemiological research. Taken together, this review presents toxicogenomic data that will be useful for improvement of the knowledge of carcinogenesis and the development of better strategies for health risk assessment.

Recent Trends in Rapid Environmental Monitoring of Pathogens and Toxicants: Potential of Nanoparticle-Based Biosensor and Applications

Of global concern, environmental pollution adversely affects human health and socioeconomic development. The presence of environmental contaminants, especially bacterial, viral, and parasitic pathogens and their toxins as well as chemical substances, poses serious public health concerns. Nanoparticle-based biosensors are considered as potential tools for rapid, specific, and highly sensitive detection of the analyte of interest (both biotic and abiotic contaminants). In particular, there are several limitations of conventional detection methods for water-borne pathogens due to low concentrations and interference with various enzymatic inhibitors in the environmental samples. The increase of cells to detection levels requires long incubation time. This review describes current state of biosensor nanotechnology, the advantage over conventional detection methods, and the challenges due to testing of environmental samples. The major approach is to use nanoparticles as signal reporter to increase output rather than spending time to increase cell concentrations. Trends in future development of novel detection devices and their advantages over other environmental monitoring methodologies are also discussed.

Influence of weathering and substrate roughness on the interfacial adhesion of acrylic coating based on an increasing load scratch test

An increasing normal load scratch test was employed to study the scratch behavior of acrylic coatings. The effects of weathering and substrate surface roughness on the interfacial adhesion of acrylic-coated thermoplastic polyolefin (TPO) systems were investigated. The increasing load test gives valuable information regarding the onset location to failure and the critical normal load for interfacial delamination. Both flatbed scanner and scanning electron microscope are utilized to characterize the scratch-induced damage mechanism of the coated TPO system. An increase in weathering time and in surface roughness of the virgin TPO leads to the increase in scratch resistance of acrylic coating. In addition, with increasing weathering time there is an increase in discoloration, while a decrease in gloss occurs. The correlation between the change of scratch coefficient of friction and the onset location of interfacial delamination is discussed.

Human AP Endonuclease 1: A Potential Marker for the Prediction of Environmental Carcinogenesis Risk

Human apurinic/apyrimidinic endonuclease 1 (APE1) functions mainly in DNA repair as an enzyme removing AP sites and in redox signaling as a coactivator of various transcription factors. Based on these multifunctions of APE1 within cells, numerous studies have reported that the alteration of APE1 could be a crucial factor in development of human diseases such as cancer and neurodegeneration. In fact, the study on the combination of an individuals genetic make-up with environmental factors (gene-environment interaction) is of great importance to understand the development of diseases, especially lethal diseases including cancer. Recent reports have suggested that the human carcinogenic risk following exposure to environmental toxicants is affected by APE1 alterations in terms of gene-environment interactions. In this review, we initially outline the critical APE1 functions in the various intracellular mechanisms including DNA repair and redox regulation and its roles in human diseases. Several findings demonstrate that the change in expression and activity as well as genetic variability of APE1 caused by environmental chemical (e.g., heavy metals and cigarette smoke) and physical carcinogens (ultraviolet and ionizing radiation) is likely associated with various cancers. These enable us to ultimately suggest APE1 as a vital marker for the prediction of environmental carcinogenesis risk.

Identification of molecular candidates and interaction networks via integrative toxicogenomic analysis in a human cell line following low-dose exposure to the carcinogenic metals cadmium and nickel.

Cadmium and nickel have been classified as carcinogenic to humans by the World Health Organizations International Agency for Research on Cancer. Given their prevalence in the environment, the fact that cadmium and nickel may cause diseases including cancer even at low doses is a cause for concern. However, the exact mechanisms underlying the toxicological effects induced by low-dose exposure to cadmium and nickel remain to be elucidated. Furthermore, it has recently been recognized that integrative analysis of DNA, mRNA and proteins is required to discover biomarkers and signaling networks relevant to human toxicant exposure. In the present study, we examined the deleterious effects of chronic low-dose exposure of either cadmium or nickel on global profiling of DNA copy number variation, mRNA and proteins. Array comparative genomic hybridization, gene expression microarray and functional proteomics were conducted, and a bioinformatics tool, which predicted signaling pathways, was applied to integrate data for each heavy metal separately and together. We found distinctive signaling networks associated with subchronic low-dose exposure to cadmium and nickel, and identified pathways common to both. ACTB, HSP90AA1, HSPA5 and HSPA8, which are key mediators of pathways related to apoptosis, proliferation and neoplastic processes, were key mediators of the same pathways in low-dose nickel and cadmium exposure in particular. CASP-associated signaling pathways involving CASP3, CASP7 and CASP9 were observed in cadmium-exposed cells. We found that HSP90AA1, one of the main modulators, interacted with HIF1A, AR and BCL2 in nickel-exposed cells. Interestingly, we found that HSP90AA1 was involved in the BCL2-associated apoptotic pathway in the nickel-only data, whereas this gene interacted with several genes functioning in CASP-associated apoptotic signaling in the cadmium-only data. Additionally, JUN and FASN were main modulators in nickel-responsive signaling pathways. Our results provide valuable biomarkers and distinctive signaling networks that responded to subchronic low-dose exposure to cadmium and nickel.

One-step synthesis of silver nanoplates with high aspect ratios: using coordination of silver ions to enhance lateral growth

The single-step production of Ag nanoplates with high aspect ratios is of great significance for their applications to bendable or stretchable electrodes, but the development of a facile synthetic method remains a great challenge. In this paper, a coordination-based strategy was successfully employed to produce, in a single step, Ag nanoplates with high aspect ratios. Optimal Ag nanoplates were synthesized in the presence of acetonitrile, which served both as the co-solvent and as the ligand to form complexes with the Ag+ ions. Coordination effect of the Ag+ ions by acetonitrile apparently decreased the rate of the reduction of these ions, leading to a decrease in the number of seeds formed in the nucleation step. Decreasing the number of seeds in this way, while keeping the concentration of the Ag precursor constant, resulted in the formation of larger Ag nanoplates. This new synthetic method specifically enabled the formation of Ag nanoplates with lateral dimensions exceeding 1 μm and with thickness values of approximately 30 nm. These Ag nanoplates were found to show electrical percolation in a short sintering time and high electrical conductivity when they were directly used as metal inks to produce conductive patterns for printed electronics.

Quantitative determination of mar resistance of high gloss coatings

Abstract

Impact performance and toughening mechanisms of toughness-tailored polypropylene impact copolymers

The impact performance and resistance of toughness-tailored polypropylene (PP) impact copolymer (ICP) blends were examined using a range of microscopic techniques. The double-notch four-point bending (DN-4PB) Charpy impact technique was used to clearly study the impact-enhancement of the ICP blends responsible for the observed toughening effect. The incorporation of ethylene–octene copolymer with a lower molecular weight into the PP matrix induced the formation of massive crazes and shear yielding, leading to a more ductile PP matrix. A detailed investigation showed that well-oriented talc particles act in the PP matrix as stress concentrators to initiate massive crazes by crack deflection and bifurcation. These toughening mechanisms are responsible for the improved impact resistance. The DN-4PB Charpy impact technique used in this study provides an effective methodology for probing the impact fracture mechanisms of toughness-tailored ICP blends.