• Molecular & Cellular Toxicology
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• 제5권4호
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• pp.310-316
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• 2009

Some environmental chemicals have been shown to cause liver-toxicity as the result of bioaccumulation. Particularly, fungicides have been shown to cause varying degrees of hepatictoxicity and to disrupt steroid hormone homeostasis in in vivo models. The principal objective of this study was to evaluate the liver-toxic responses of environmental chemicals-in this case selected fungicides and parasiticides-in order to determine whether or not this agent differentially affected its toxicogenomic activities in hepatic tumor cell lines. To determine the gene expression profiles of 3 fungicides (triadimefon, myclobutanil, vinclozolin) and 1 parasiticide (dibutyl phthalate), we utilized a modified HazChem human array V2. Additionally, in order to observe the differential alterations in its time-dependent activities, we conducted two time (3 hr, 48 hr) exposures to the respective IC20 values of four chemicals. As a result, we analyzed the expression profiles of a total of 1638 genes, and we identified 70 positive significant genes and 144 negative significant genes using four fungicidic and parasiticidic chemicals, using SAM (Significant Analysis of Microarray) methods (q-value<0.5%). These genes were analyzed and identified as being related to apoptosis, stress responses, germ cell development, cofactor metabolism, and lipid metabolism in GO functions and pathways. Additionally, we found 120 genes among those time-dependently differentially expressed genes, using 1-way ANOVA (P-value<0.05). These genes were related to protein metabolism, stress responses, and positive regulation of apoptosis. These data support the conclusion that the four tested chemicals have common toxicogenomic effects and evidence respectively differential expression profiles according to exposure time.

• 한국환경성돌연변이발암원학회지
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• 제24권2호
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• pp.91-98
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• 2004

Although 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD) is a powerful carcinogen in several species, limited model system exist to study carcinogenicity of this compound at cellular level. To enhance our under-standing of carcinogenicity of TCDD at cellular level, we investigated micronucleus (MN) frequency as a index of genetic toxicity and whether TCDD can transform the human cells in culture. Normal human cell lines, skin keratinocyte HaCaT, Chang liver and breast MCF10A cells were used. TCDD did not affect the cell viability of the Chang liver, HaCaT and MCF10A cells. The frequency of micronucleus was increased after treatment of TCDD for 24hr in Chang liver and HaCaT cells, but not changed in MCF10A cells. And we observed putative transformed cells in Chang liver cells exposed to 1 $\mu$M TCDD for 2 weeks. The putative transformed cells were also observed in HaCaT cells with subsequent exposure to TCDD (0.1, 1, 10, 100 nM) for 2 weeks after initial exposure to MNNG, but not observed in MCF10A cells. Collectively, these results indicate that the ability of TCDD to induce micronuclei may be involved in cellular transformation of Chang liver and HaCaT cells. Our putative TCDD-transformed cells of Chang liver and HaCaT are expected to provide a clue to the elucidation of TCDD-induced transformation pathway.

• 대한한방종양학회지
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• 제7권1호
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• pp.1-18
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• 2001

Objective: This experimental study was carried out to evaluate the effects of Saussurea Radix and Plantaginis Herba on cellular viability, proliferation, apoptosis and expression of the cell cycle-related genes in cultured gastric cancer cells. Method :MTT assay for analysis of cellular toxicity and the effect on suppression of cellular viability, $[^{3}H]$ thymidine incorporation assay for evaluation of the effect on suppression of DNA replication, tryphan blue exclusion assay for measurement of induction of apoptosis and Quantitative RT-PCR for analysis of the effects on expression of cell cycle or apoptosis-related genes were performed. Results: Antitumor activity of Saussurea Radix associated with inhibition of cell cycle progression and promotion of apoptosis caused by transcriptional regulation of p53, p21/Wafl and the other related genes was observed.

• Entomological Research
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• 제48권6호
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• pp.533-539
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• 2018

The RNA interference (RNAi) has been considered as an important genetic tool and applied to develop a new living modified (LM) crop trait which is an improvement of nutrient quality or pest management. The RNAi of DvSnf7 has been used for resistance to LM maize and the Western Corn Rootworm which is a major agricultural pest for the US Corn Belt. Most of the environmental risk assessments (ERA) of double strand RNA (dsRNA) have been performed using in vitro transcript products, and not in vivo expressed product. A large amount of dsRNA was required for the acute toxicity assay of water fleas. Therefore development of massive dsRNA purification techniques is critical. Daphnia, a freshwater microcrustacean, is a model organism for studying cellular and molecular mechanism involved in life history traits and ecotoxicology. In this study, we established the massive dsRNA purification method using Escherichia coli and implemented acute toxicity assays to Daphnia magna. As a result, the present RNase A and DNase I, dsRNA was efficiently purified without any special techniques or equipment. Even though purified dsRNA existed during the acute toxicity test, lethality or abnormal behavior were not observed in D. magna. These results indicated that GFP and DvSnf7 dsRNA were not significantly affected to D. magna due to their lack of sequence matching in its genome. The purification method of dsRNA and the acute toxicity assay of water fleas using purified dsRNA would be suitable for the toxicological studies of LMOs to aquatic non-target organisms.

• 환경생물
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• 제27권4호
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• pp.323-333
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• 2009

파라벤은 p-하이드록시 벤조산(p-hydroxybenzoic acid)의 알킬에스테르로, 비교적 빠르게 흡수, 대사 및 배설되는 살균성 보존제로 식품, 화장품, 약품 등에 널리 사용되고 있다. 실제 인체는 파라벤 복합물에 노출된다. 파라벤의 안전성에 관한 연구결과들에 대한 고찰 결과 파라벤 종류에 따라 다양한 독성종말점을 대상으로 파라벤의 급성, 아급성 및 만성독성 영향은 비교적 적은 것으로 나타났다. 파라벤은 에스트로젠 유사활성을 가지며 화장품을 통한 경피흡수를 통해 유방암과의 상관성이 보고되었으나, 이와 상반된 견해도 있다. 파라벤의 항안드로젠성은 남성생식기계의 장애를 유발할 수 있으나 이와 상반된 견해도 있다. 파라벤은 정자의 미토콘드리아 기능 및 남성호르몬 생성을 저해할 수 있으나 이와 상반된 견해도 있다. 배아발달에는 독성이 없는 것으로 나타났다. 세포독성으로는 세포용혈, 미토콘드리아 막투과성 변화, 세포사멸 등을 유발할 수 있다. 수환경에서 파라벤은 환경에스트로젠으로 작동하여 어류에서 내분비장애 효과를 발휘한다. 결론적으로 파라벤은 저독성물질로 분류할 수 있으나, 인체 및 수생동물들에서 파라벤의 노출경로 및 농도, 사용기간 등에 따른 독성과 내분비계장애 효과에 대하여는 다양한 종말점을 대상으로 좀 더 구체적인 독성자료들이 요구된다.

• Mycobiology
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• 제45권4호
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• pp.233-239
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• 2017

Drosophila melanogaster is a useful model organism that offers essential insights into developmental and cellular processes shared with humans, which has been adapted for large scale analysis of medically important microbes and to test the toxicity of heavy metals, industrial solvents and other poisonous substances. We here give a brief review of the use of the Drosophila model in medical mycology, discuss the volatile organic compounds (VOCs) produced by the opportunistic human pathogen, Aspergillus fumigatus, and give a brief summary of what is known about the toxicity of some common fungal VOCs. Further, we discuss the use of VOC detection as an indirect indicator of fungal growth, including for early diagnosis of aspergillosis. Finally, we hypothesize that D. melanogaster has promise for investigating the role of VOCs synthesized by A. fumigatus as possible virulence factors.

• Toxicological Research
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• 제30권4호
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• pp.221-234
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• 2014

Mitochondria dysfunction was first described in the 1960s. However, the extent and mechanisms of mitochondria dysfunction's role in cellular physiology and pathology has only recently begun to be appreciated. To adequately evaluate mitochondria-mediated toxicity, it is not only necessary to understand mitochondria biology, but discerning mitochondrial redox biology is also essential. The latter is intricately tied to mitochondrial bioenergetics. Mitochondrial free radicals, antioxidants, and antioxidant enzymes are players in mitochondrial redox biology. This review will provide an across-the-board, albeit not in-depth, overview of mitochondria biology and mitochondrial redox biology. With accumulating knowledge on mitochondria biology and mitochondrial redox biology, we may devise experimental methods with adequate sensitivity and specificity to evaluate mitochondrial toxicity, especially in vivo in living organisms, in the near future.

• 대한의생명과학회지
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• 제27권3호
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• pp.111-120
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• 2021

Asbestos products had been widely used until 2007 in Korea since the 1930s. A total ban on their production and applications has been imposed because of the toxic effect of asbestos fibers on the human health. The inhaled asbestos fibers increase reactive oxygen species and inflammatory reactions in the respiratory airway including the alveolar sac, resulting in DNA damages and secretion of several inflammatory cytokines or chemokines. These paracrine communications promote the proliferation of fibroblasts and the synthesis of collagen fibers, thereby depositing them into the extracellular matrix at the interstitial space of alveoli. The fibrotic tissue hindered the gas exchange in the alveolus. This reviews describes not only the cytotoxic effects of asbestos fibers with different physical or chemical characteristics but also the interaction of cells that make up the respiratory airway to understand the molecular or cellular mechanisms of asbestos fiber-induced toxicity. In addition, we propose a pulmonary toxicity research technique based on the mini-lung that can mimic human respiratory system as an alternative to overcome the limitations of the conventional risk assessment of asbestos fibers.

• Molecular & Cellular Toxicology
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• 제1권3호
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• pp.179-188
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• 2005

To develop the novel anti-allergic drug, many sophoricoside derivatives were synthesized. Among these derivatives, JSH-II-3, VI-3, VII-3, VIII-3, VII-20 and VII-20 (sodium salt) were selected and subjected to high throughput toxicity screening (HTTS) because they revealed strong IL-5 inhibitory activity and limitation of quantity. Single cell gel electrophoresis (Comet) assay, mouse lymphoma thymidine kinase ($tk^{+/-}$) gene assay (MOLY), chromosomal aberration assay in mammalian cells and Ames reverse mutation assay in bacterial system were used as simplified, inexpensive, short-term in vitro screening tests in our laboratory. Through the primary screening using the comet assay, we could choose the first candidates of sophoricoside derivatives with no genotoxic potentials as JSH-VI-3, VII-3, VII-20 and VII-20 (sodium salt). Also JSH-VII-3, VII-20 and VII-20 (sodium salt) are non-mutagenic in MOLY assay, while JSH-II-3 is mutagenic at high concentration with the presence of metabolic activation system in both comet assay and MOLY assay. The selected derivatives (JSH-VI-3, VII-3, VII-20 and VII-20 (sodium salt) are not mutagenic in S. typhimurium TA98 and TA100 strains both in the presence and absence of metabolic activation. From results of chromosomal aberration assay, 6 h treatment of JSH-VI-3, VII-3 and VII-20 (sodium salt) were not revealed clastogenicity both in the presence and absence of S-9 mixture. Therefore, we suggests that JSH-VI-3, VII-3, VII-20 and VII-20 (sodium salt), as the optimal candidates with both no genotoxic potential and IL-5 inhibitory effects must be chosen. To process the development into new anti-inflammatory drug of these derivatives, further investigation will need.

• Molecular & Cellular Toxicology
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• 제4권3호
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• pp.183-191
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• 2008

Volatile organic compounds (VOCs) are common constituents of cleaning and degreasing agents, paints, pesticides, personal care products, gasoline and solvents. And VOCs are evaporated at room temperature and most of them exhibit acute and chronic toxicity to human. Benzene is the most widely used prototypical VOC and the toxic mechanisms of them are still unclear. The multi-step process of toxic mechanism can be more fully understood by characterizing gene expression changes induced in cells by toxicants. In this study, DNA microarray was used to monitor the expression levels of genes in HepG2 cells and HL-60 cells exposed to the benzene on IC20 and IC50 dose respectively. In the clustering analysis of gene expression profiles, although clusters of HepG2 and HL-60 cells by benzene were divided differently, expression pattern of many genes observed similarly. We identified 916 up-regulated genes and 1,144 down-regulated genes in HepG2 cells and also 1,002 up-regulated genes and 919 down-regulated genes in HL-60 cells. The gene ontology analysis on genes expressed by benzene in HepG2 and HL-60 cells, respectively, was performed. Thus, we found some principal pathways, such as, focal adhesion, gap junction and signaling pathway in HepG2 cells and toll-like receptor signaling pathway, MAPK signaling pathway, p53 signaling pathway and neuroactive ligand-receptor interaction in HL-60 cells. And we also found 16 up-regulated and 14 down-regulated commonly expressed total 30 genes that belong in the same biological process like inflammatory response, cell cycle arrest, cell migration, transmission of nerve impulse and cell motility in two cell lines. In conclusion, we suggest that this study is meaningful because these genes regarded as strong potential biomarkers of benzene independent of cell type.