Kyung-Taek Rim

Oxidative DNA Damage from Nanoparticle Exposure and Its Application to Workers' Health: A Literature Review

The use of nanoparticles (NPs) in industry is increasing, bringing with it a number of adverse health effects on workers. Like other chemical carcinogens, NPs can cause cancer via oxidative DNA damage. Of all the molecules vulnerable to oxidative modification by NPs, DNA has received the greatest attention, and biomarkers of exposure and effect are nearing validation. This review concentrates on studies published between 2000 and 2012 that attempted to detect oxidative DNA damage in humans, laboratory animals, and cell lines. It is important to review these studies to improve the current understanding of the oxidative DNA damage caused by NP exposure in the workplace. In addition to examining studies on oxidative damage, this review briefly describes NPs, giving some examples of their adverse effects, and reviews occupational exposure assessments and approaches to minimizing exposure (e.g., personal protective equipment and engineering controls such as fume hoods). Current recommendations to minimize exposure are largely based on common sense, analogy to ultrafine material toxicity, and general health and safety recommendations.

Gene-expression profiling using suppression-subtractive hybridization and cDNA microarray in rat mononuclear cells in response to welding-fume exposure:

Welders with radiographic pneumoconiosis abnormalities have shown a gradual clearing of the X-ray identified effects following removal from exposure. In some cases, the pulmonary fibrosis associated with welding fumes appears in a more severe form in welders. Accordingly, for the early detection of welding-fume-exposure-induced pulmonary fibrosis, the gene expression profiles of peripheral mononuclear cells from rats exposed to welding fumes were studied using suppression-subtractive hybridization (SSH) and a cDNA microarray. As such, Sprague-Dawley rats were exposed to a stainless steel arc welding fume for 2 h/day in an inhalation chamber with a 107.59 / 2.6 mg/m3 concentration of total suspended particulate (TSP) for 30 days. Thereafter, the total RNA was extracted from the peripheral blood mononuclear cells, the cDNA synthesized from the total RNA using the SMARTTM PCR cDNA method, and SSH performed to select the welding-fume-exposure-regulated genes. The cDNAs identified by the SSH were then cloned into a plasmid miniprep, sequenced and the sequences analysed using the NCBI BLAST programme. In the SSH cloned cDNA microarray analysis, five genes were found to increase their expression by 1.9-fold or more, including Rgs 14, which plays an important function in cellular signal transduction pathways; meanwhile 36 genes remained the same and 30 genes decreased their expression by more than 59%, including genes associated with the immune response, transcription factors and tyrosine kinases. Among the 5200 genes analysed, 256 genes (5.1%) were found to increase their gene expression, while 742 genes (15%) decreased their gene expression in response to the welding-fume exposure when tested using a commercial 5.0k DNA microarray. Therefore, unlike exposure to other toxic substances, prolonged welding-fume exposure was found to substantially downregulate many genes.

Gene-expression profiling of human mononuclear cells from welders using cDNA microarray.

A toxicogenomic chip developed to detect welding-related diseases was tested and validated for field trials. To verify the suitability of the microarray, white blood cells (WBC) or whole blood was purified and characterized from 20 subjects in the control group (average work experience of 7 yr) and 20 welders in the welding-fume exposed group (welders with an average work experience of 23 yr). Two hundred and fifty-three rat genes homologous to human genes were obtained and spotted on the chip slide. Meanwhile, a human cDNA chip spotted with 8600 human genes was also used to detect any increased or decreased levels of gene expression among the welders. After comparing the levels of gene expression between the control and welder groups using the toxicogenomic chips, 103 genes were identified as likely to be specifically changed by welding-fume exposure. Eighteen of the 253 rat genes were specifically changed in the welders, while 103 genes from the human cDNA chip were specifically changed. The genes specifically expressed by the welders were associated with inflammatory responses, toxic chemical metabolism, stress proteins, transcription factors, and signal transduction. In contrast, there was no significant change in the genes related to short-term welding-fume exposure, such as tumor necrosis factor (TNF)-alpha and interleukin. In conclusion, if further validation studies are conducted, the present toxicogenomic gene chips could be used for the effective monitoring of welding-fume-exposure-related diseases among welders.

Effect of Nano-sized Carbon Black Particles on Lung and Circulatory System by Inhalation Exposure in Rats

Objectives We sought to establish a novel method to generate nano-sized carbon black particles (nano-CBPs) with an average size smaller than 100 nm for examining the inhalation exposure risks of experimental rats. We also tested the effect of nano-CBPs on the pulmonary and circulatory systems. Methods We used chemical vapor deposition (CVD) without the addition of any additives to generate nano-CBPs with a particle size (electrical mobility diameter) of less than 100nm to examine the effects of inhalation exposure. Nano-CBPs were applied to a nose-only inhalation chamber system for studying the inhalation toxicity in rats. The effect on the lungs and circulatory system was determined according to the degree of inflammation as quantified by bronchoalveolar lavage fluid (BALF). The functional alteration of the hemostatic and vasomotor activities was measured by plasma coagulation, platelet activity, contraction and relaxation of blood vessels. Results Nano-CBPs were generated in the range of 83.3-87.9 nm. Rats were exposed for 4 hour/day, 5 days/week for 4 weeks to 4.2 × 106, 6.2 × 105, and 1.3 × 105 particles/cm3. Exposure of nano-CBPs by inhalation resulted in minimal pulmonary inflammation and did not appear to damage the lung tissue. In addition, there was no significant effect on blood functions, such as plasma coagulation and platelet aggregation, or on vasomotor function. Conclusion We successfully generated nano-CBPs in the range of 83.3-87.9 nm at a maximum concentration of 4.2 × 106 particles/cm3 in a nose-only inhalation chamber system. This reliable method can be useful to investigate the biological and toxicological effects of inhalation exposure to nano-CBPs on experimental rats.

Effects of rare earth elements on the environment and human health: A literature review

REEs are a group of metals comprised of yttrium, fourteen lanthanide elements, and scandium, which have been called ‘industrial vitamins’ and a ‘treasury’ of novel materials due to their dominant role in technical progress and in the development of traditional industries. Despite the growing interest, information that has become available over the last two decades regarding RREs is relatively premature and scarce, which has led to the current controversy regarding the health benefits vs toxic effects of these materials. There are many environmental and health issues associated the production, processing, and utilization of REEs. This review offers an examination of the roles of REEs in the onset of cellular oxidative stress in reference to the impact of REE exposure to cells, animals, and plants, in order to explain disease and occupational poisoning of local residents, water pollution, and farmland destruction. Conversely, a body of evidence has shown REE-associated antioxidant effects in the treatment of many diseases. The content herein is aimed at presenting the recent and pending developments in the field of REE with respect to environmental and human health implications. Multi-faceted updates on the roles of REEs focusing on different organisms and exposure routes, and several issues regarding environmental and biological research, are discussed. The current gaps in information raise a number of open questions that deserve ad hoc investigation.

Biologically hazardous agents at work and efforts to protect workers' health: a review of recent reports.

Abstract Because information on biological agents in the workplace is lacking, biological hazard analyses at the workplace to securely recognize the harmful factors with biological basis are desperately needed. This review concentrates on literatures published after 2010 that attempted to detect biological hazards to humans, especially workers, and the efforts to protect them against these factors. It is important to improve the current understanding of the health hazards caused by biological factors at the workplace. In addition, this review briefly describes these factors and provides some examples of their adverse health effects. It also reviews risk assessments, protection with personal protective equipment, prevention with training of workers, regulations, as well as vaccinations.

Toxicological evaluation of MSG for the manufacturing workers’ health: A literature review

In spite of the controversies over safety of MSG, monosodium glutamate (MSG), a flavor enhancer, has not yet been generally accepted to be toxic to humans, but also being produced in large quantities throughout the world. Occupational risk assessment or health hazards evaluation associated with MSG products including engineering controls have rarely been studied. Current recommendations to minimize exposure and hazards to establish and maintain a safe working environment are largely based on scientific evidence of its mutagenicity; however, additional study is needed to assess the risks for workers, as well as to measure the MSG levels in the workplace. This review deems some of the points behind the application to health and safety in MSG manufacturing workers. The use of biomarkers is increasing as a sustainable measure for the establishment of a safe workplaces because of growing demands for preventing unfavorable exposure. With respect to the future prospects of MSG production, the overall effect of MSG on the environment, workplace, and occupational health concerns must be investigated in detail.

Effects of carbon black to inflammation and oxidative DNA damages in mouse macrophages

Carbon black is classified as carcinogen group 2B by International Agency for Research on Cancer (IARC). But it uncertained the effects of ultrafine carbon black particles on oxidative damage or inflammation. So we were focused to evaluate the oxidative damage or inflammation with ultrafine carbon black particles at gene expression level by using mouse macrophage cell line, and the co-effects with solvent coating to it. It was evaluated the changes of gene expression with real time RT-PCR, and oxidative DNA damage with Fragment Length Analysis with Restriction Enzyme (FLARE) assay in mouse macrophage (RAW264.7) cell line. Two kinds of carbon black induced the gene expression of cytokines related to acute inflammation, and with 0.1% methylcyclohexane coating were regulated conversely each other. The oxidative DNA damage with smaller size carbon black was increased than bigger one (the range with 500–30 nm). The 0.1% methylcyclohexane increased the damage by binding with each carbon black (the dose range with 100 ng/mL-100 μg/mL). In this study, we got the conclusion that the genotoxicity of carbon blacks are elevated with its size get smaller and their surface area wider, and with methylcyclohexane coating. It could cause DNA damage by promoting oxidative stress and inflammatory responses.

Effect of cerium oxide nanoparticles to inflammation and oxidative DNA damages in H9c2 cells

Occupational heart disease have occurred continuously, making social problems, and increasing the needs for its effective prevention. As natural antioxidants, selenium (Na2SeO3) and cerium oxide (CeO2) nanoparticles, we verified the effect with suspected cardiotoxic chemicals, 1,1,1-trichloroethane (TCEtn) based on the myocardial cell line due to inflammation and oxidative DNA damage, and reliable anti-cardiotoxic effects of selenium and CeO2 nanoparticles. We measured the changes of gene expression with real-time RT-PCR, and oxidative DNA damage with Fragment Length Analysis with Restriction Enzyme (FLARE) assay in H9c2 cell line, and discuss their molecular mechanism from these data. In the result, it has anticytotoxic effect with CeO2 nanoparticles below 100 μM which the particles dispersed well. The early expression of COX2 mRNA is increased with TCEtn but decreased with Na2SeO3, CeO2 nanoparticles, has some anti-inflammatory effect. The PPARγ is much increased with all of TCEtn, Na2SeO3, CeO2 nanoparticles in 36 hour pretreat, are evaluated their activation to cytokines, transcription factors related to overcome and decrease the cardiotoxic effects of test chemical. With the oxidative DNA damage, the CeO2 nanoparticles have more active anti-oxidative effect to selenium.

A Study of Micronucleus Induction with Methyl Formate and 2-Methylbutane in Bone Marrow Cells of Male ICR Mice

Objectives We investigated the genotoxicity of two chemicals, methyl formate and 2-methylbutane, using male ICR mice bone marrow cells for the screening of micronucleus induction. Although these two chemicals have already been tested numerous times, a micronucleus test has not been conducted and the amounts used have recently been increased. Methods 7 week male ICR mice were tested at dosages of 250, 500, and 1,000 mg/kg for methyl formate and 500, 1,000, and 2,000 mg/kg for 2-methlybutane, respectively. After 24 hours of oral administration with the two chemicals, the mice were sacrificed and their bone marrow cells were prepared for smearing slides. Results As a result of counting the micronucleated polychromatic erythrocyte (MNPCE) of 2,000 polychromatic erythrocytes, all treated groups expressed no statistically significant increase of MNPCE compared to the negative control group. There were no clinical signs related with the oral exposure of these two chemicals. Conclusion It was concluded that the two chemicals did not induce micronucleus in the bone marrow cells of ICR mice, and there was no direct proportion with dosage. These results indicate that the two chemicals have no mutagenic potential under each study condition.