• Molecular & Cellular Toxicology
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• 제5권3호
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• pp.243-249
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• 2009

Melamine, which is used to produce melamine resin for various industrial applications, has a high nitrogen content by mass. For this reason, it has been illegally added to foods to increase their apparent protein content. In the present investigation, melamine-induced oxidative damage of human lymphocyte DNA was evaluated by Comet assay. The in vitro oxidative DNA damage caused by melamine increased in a dose-dependent manner. This DNA damage was significantly inhibited by treatment with ascorbate. Moreover, the traditional Korean medicinal herb, named Acanthopanax, red ginseng and green tea markedly reduced the DNA damage. Various edible plant extracts also inhibited melamine-induced oxidative DNA damage in vitro. Melamine enhanced intracellular ROS generation, and this effect was suppressed by treatment with various antioxidants.

• Molecular & Cellular Toxicology
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• 제3권3호
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• pp.172-176
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• 2007

Butylated hydroxytoluene (BHT) is widely used antioxidant food additives. It has been extensively studied for potential toxicities. BHT appears adverse effects in liver and thyroid. In this study, we evaluated the genetic toxicity of BHT with more advanced methods, in vitro mouse lymphoma assay $tk^{+/-}$ gene assay (MLA) and in vivo mouse supravital micronucleus (MN) assay. BHT did not appear the significantly results in the absence and presence of metabolic activation system with MLA. Also, in vivo testing of BHT yielded negative results with supravital MN assay. These results suggest that BHT itself was not generally considered genotoxic.

• Toxicological Research
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• 제22권4호
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• pp.323-328
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• 2006

Global gene expression profile was analyzed by microarray analysis of rat liver RNA after acute acetaminophen (APAP) administration. A single dose of 1g/kg body weight of APAP was given orally, and the liver samples were obtained after 24, 48 h, and 2 weeks. Histopathologic and biochemical studies enabled the classification of the APAP effect into injury (24 and 48 h) and regeneration (2 weeks) stages. The expression levels of 4900 clones on a custom rat gene microarray were analyzed and 484 clones were differentially expressed with more than a 1.625-fold difference(which equals 0.7 in log2 scale) at one or more time points. Two hundred ninety seven clones were classified as injury-specific clones, while 149 clones as regeneration-specific ones. Characteristic gene expression profiles could be associated with APAP-induced gene expression changes in lipid metabolism, stress response, and protein metabolism. We established a global gene expression profile utilizing microarray analysis in rat liver upon acute APAP administration with a full chronological profile that not only covers injury stage but also later point of regeneration stage.

• Molecular & Cellular Toxicology
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• 제2권3호
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• pp.216-221
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• 2006

The cholinesterase-inhibiting organophosphorous (OP) compounds known as nerve agents are highly toxic. The principal toxic mechanism of OP compounds is the inhibition of acethylcholine esterase (AChE) by phosphorylation of its catalytic site. The reversible competitive inhibition of AChE may prevent the subsequent OP intoxication. In this study, three-dimensional quantitative structure-activity relationship (3D-QSAR) was performed to investigate the relationship between the 29 compounds with structural diversity and their bioactivities against AChE. In particular, predictive models were constructed using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The results indicate reasonable model for CoMFA ($q^{2}=0.453,\;r^{2}=0.697$) and CoMSIA ($q^{2}=0.518,\;r^{2}=0.696$). The presence of steric and hydophobic group at naphtyl moiety of the model may lead to the design of improved competitive inhibitors for organophosphorous intoxication.

• Molecular & Cellular Toxicology
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• 제1권4호
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• pp.262-267
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• 2005

Using genetic engineering, the Vitreoscilla (bacterial) hemoglobin gene (vgb) was integrated stably into the chromosomes of and Burkholderia cepacia. Similar to previous results, the wild type VHb improved growth for Burkholderia cepacia and degradation of benzoic acid under both normal and low aeration conditions. The stable expression of VHb enhanced these parameters. The results demonstrate the possibility that the positive effects provided by VHb may be augmented by protein engineering.

• Molecular & Cellular Toxicology
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• 제3권2호
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• pp.77-84
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• 2007

Millions of individuals worldwide are currently afflicted with neurodegenerative disorders such as Parkinson's disease and multiple sclerosis which are caused by the death of specific types of specialized cells in the Central Nervous System (CNS). Recently, Neural Stem Cells (NSCs) are able to replace these dead cells with new functional cells, thereby providing a cure for devastating neural diseases. The clinical use of neural stem cells (NSCs) for the treatment of neurological diseases requires overcoming the scarcity of the initial in vivo NSC population. Thus, we developed a novel 3-dimentional cellular automata model for optimum production of neural stem cells and their derivatives in large scale to treat neurodegenerative disorder patients.

• Molecular & Cellular Toxicology
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• 제3권2호
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• pp.145-149
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• 2007

Studies of relationship between structure and toxicity of azo dyes have been performed with comparative molecular field analysis (CoMFA) techniques. 3D QSTR analyses indicate that the steric and electrostatic interactions are important. The steric field based model gives strong correlation ($q^2$=0.57, $r^2$= 0.92). The steric field in conjunction with electrostatic field give more strong correlation ($q^2$=0.57, $r^2$=0.95). All study indicates that a bulky and electronegative group at benzene ring and a small group at position 3 of aniline ring might be significant to reduce the mutagenicity.

• Molecular & Cellular Toxicology
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• 제3권2호
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• pp.113-118
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• 2007

Chlorobenzenes due to their acute toxicity and the capability of bioaccumulating are of great health and environmental concern. Especially, 1, 2-dichlorobenzene (CAS No. 95-50-1) is used for organic synthesis, dye manufacture, as a solvent and for other applications in chemical industry. Adverse effects of 1, 2-dichlorobenzene includes increases in liver and kidney weights and hepatotoxicity. In this study, we evaluated the genetic toxicity of 1, 2-dichlorobenzene with more advanced methods, in vitro mouse lymphoma assay $tk^{+/-}$ gene assay (MLA) and in vitro mouse supravital micronucleus (MN) assay. 1, 2-Dichlorobenzene appeared the significantly positive results and the induction of large mutant colonies only in the presence of metabolic activation system with MLA. But in vitro testing of 1, 2-dichlorobenzene yielded negative results with supravital MN assay. These results suggest that 1, 2-dichlorobenzene may play a mutagen rather than clastogen in vitro mammalian system.

• Molecular & Cellular Toxicology
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• 제4권4호
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• pp.300-306
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• 2008

We investigated high light-induced alterations in antioxidant enzymes by exposing green vegetative cells of the alga Haematococcus pluvialis to excess irradiance to induce the production of astaxanthin, a carotenoid pigment. Total activity of catalase decreased approximately 70% after high light exposure, whereas glutathione peroxidase (GPX) activity was slightly enhanced. Total activity of superoxide dismutase and ascorbate peroxidase (APX) also slightly decreased. Overall, we did not observe dramatically elevated levels of antioxidant isozymes, although APXn, GPX2, and GPX3 isozyme increased slightly. ${H_2}{O_2}$ content increased about sixfold after high light exposure, demonstrating severe cellular oxidative stress, whereas lipid peroxidation was notably reduced. Concomitantly, astaxanthin accumulation increased about sevenfold. This result suggests that probably massively accumulated astaxanthin may be one of the antioxidant protector against high light stress.

• Molecular & Cellular Toxicology
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• 제4권4호
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• pp.311-317
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• 2008

Zebrafish were exposed to commercial silver nanoparticles (${\sim}$10-20 nm) at 0.4 and 4 ppm during cadual fin regeneration. The silver was in the $Ag^+$ ionic form. Fin regeneration was slow in the group exposed to the lower concentration. The cadual fin, gill, and muscle were assayed after 48 hours and subjected to histological analysis. In all tissues sampled, fish exposed to nanoparticles exhibited infiltration, large mitochondria with empty matrices, and accumulation of nano-sized silver in blood vessels. The results suggested mitochondrial damage and induction of inflammation. Microarray analysis of RNA from young zebrafish (52 hours post-fertilization) that were exposed to nanometer-sized silver particles, showed alteration in expression of the p53 gene pathway related to apoptosis. Gene expression changes in the nanoparticle-treated zebrafish led to phenotypic changes, reflecting increased apoptosis.