Ceramide, a potential cell death marker formed by sphingomyelinase, is involved in the expression of cyclooxygenase-2 (COX-2). This study examines the effect of C2-ceramide (C2), a cell-permeable ceramide analog, on the LPS-inducible COX-2 expression and signaling pathways. C2 did not induce COX-2, but potentiated LPS-inducible COX-2 expression in Raw264.7 cells, whereas dihydro-C2 was inactive.(omitted)

Molecular immunological methods are extensively applied to toxicological investigations. Furthermore, various immunological markers have been developed to substantiate molecular mechanisms of xenobiotics-mediated immunotoxicities. We discuss molecular immunological approach to evaluate lead (Pb)-induced immune alteration resulting in suppression of IFN${\gamma}$ production, and its value for establishing useful immunotoxicological markers.(omitted)

Arylamines are suspected to be the primary causative agent of urothelial cancer in tobacco smoke. In the human liver, arylamines are N-hydroxylated by a cytochrome P450 (CYP) 1A2-catalyzed reaction, which produces a substrate for O-esterification that can be catalyzed by N-acetylatransferases (NAT) or sulfotransferases (SULT). (omitted)

Oxidative stress is the hallmark of various inflammatory lung diseases/disorders such as asthma, adult respiratory distress syndrome, idiopathic pulmonary fibrosis, pneumonia, lung transplantation, Chronic Obstructive Pulmonary Disease (COPD), cystic fibrosis, bronchiectasis, lung cancer and various occupational diseases. (omitted)

There is increasing interest in the involvement of transcription factors, such as of the transcription factor NF-kB (nuclear factor-kB), in the pathogenesis of various diseases. The involvement ofNF-kB is especially of interest as it is activated by oxidative stress and its activation can be modulated by antioxidant compounds. (omitted)

It is widely accepted that free-radical induced oxidative damages are involved in pathogenic processes of major diseases including cancer, atherosclerosis, rheumatoid arthritis and diabetes. A number of epidemiological studies have indicated that frequent consumptions of plant foods rich in antioxidants reduce the risk of developing cancer and cardiovascular diseases, while many intervention trials have failed to prove the protective role of major dietary antioxidants.(omitted)

The heavy metal cadmium is a xenobiotic toxicant of environmental and occupational concern and it has been classified as a human carcinogen. Inhalation of cadmiumhas been implicated in the development of emphysema and pulmonary fibrosis, but, the detailed mechanism by which cadmium induces adverse biological effects is not yet known.(omitted)

The monitoring of genotoxic effect or oxidative DNA damage in workers exposed to hazardous materials is increasingly applied for hazard identification or risk assessment purposes in workplaces. The current generation of biomarkers has the potential to allow for the earlier detection of occupational disease, for the reduction of misclassification of exposure and outcome. (omitted)

The potential application of toxicogenomics to predictive toxicology has been discussed widely, but the utility of the approach remains largely unproven. Using cDNA microarrays, we have compared the gene expression profiles produced in mouse lymphoma cells by three genotoxic compounds, hydroxyurea (a carcino- gen), p-anisidine (a noncarcinogen) and paclitaxel (carcinogenicity unknown). (omitted)

High iron consumption is associated with an increased risk of cancer possibly via production of reactive oxygen species (ROS) which in turn induces oxidative damage to lipids, proteins and DNA. The aim of the study was to determine whether Fe-NT A causes DNA damage and targets TP 53 in human peripheral lymphocytes. (omitted)

Ochratoxin A (OA), a potent nephrotoxin in several species, is knownto be a renal carcinogen in animals and is implicated in the etiology of Balkan endemic nephropathy (BEN). The NTP (National Toxicology Program) classified Ochratoxin A as having clear evidence of carcinogenic activity, based on uncommon tubular adenomas and tubular cell carcinomas of the kidney and multiple fibroadenomas of the mammary gland, seen in the rat.(omitted)

Matrix metalloproteinases (MMPs) inhibitors were screened from Metasequoia glyptostroboides and one potent inhibitor, dihydrohinokiflavone (DHHF), a biflavonoid, was selected. DHHF inhibited proliferation of HT1080, human fibrosarcoma cells in a dose-dependent manner. Noncytotoxic levels of DHHF dramatically decreased MMP-9 and MMP-2 production in unistimulated cells, but did not change the level of tissue inhibited of metalloproteinase (TIMP)-1, an inhibitor of MMP-9.(omitted)

The subacute toxicity and toxicokinetics of a type IV phosphodiesterase inhibitor, CJ-10882, were evaluated after single (on the 1st day) and 4-week (on the 27th day) oral administration of the drug, in doses of 0 (to serve as a control), 2, 10 and 50 mg/kg/d, to male and female dogs (n = 3 for male and female dogs for each dose). During the test period, clinical signs, mortality, body weight, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weight and histopathology were examined.(omitted)

The present study was conducted to investigate the potential embryo-fetal toxicity of Artesunate, an antimalarial drug, in Sprague-Dawley rats. The test item was orally administered by gavage to pregnant rats (22 females per group) from days 6 through 15 of gestation at dose levels of 0, 2, 4 and 8 mg/kg/ day. (omitted)

The present study examined the effect of alcohol extract of Isaria sinclairii on blood pressure in spontaneously hypertensive rats (SHR). The blood pressure and heart rate were measured after treatment of alcohol extract of Isaria sinclairii by indirect tail cuff method and direct in vivo model. Male SHR were treated with extracts for 2 or 4 weeks starting at 12 weeks of age. (omitted)

Acridine orange를 이용한 염색법은 OECD guideline 474에 채택되어 널리 사용되고 있는 염색법으로 Giemsa를 이용하였을 때 보다 artifact를 구별하기 쉬우며 숙련되지 않는 관찰자도 쉽게 소핵을 구별할 수 있다는 장점을 가지고 있다. 본 시험에서는 신약의 초기 screening단계에서 유전독성여부를 알아보기 위한 방법으로 마우스 골수세포와 말초혈액을 이용하여 Geimsa와 Acridine orange염색법을 비교하였다. (중략)

Toxicogenomics is a term that represents the merging of toxicology with novel genomics techniques. Microarray, which provides a revolutionary basis to perform global gene expression analyses and to decode biological pathways, has begun to have a major impact on many different fields of drug discovery and development. (omitted)

Nitric oxide (NO) has been studied and found to be an important intracellular modulator. The excess NO produced by the inducible nitric-oxide synthase (iNOS) is implicated in various inflammatory diseases and cellular injury. Inflammatory cytokines such as TNF- or IL-6 increase intracellular ceramide and ceramide may induce NO production and inflammation. (omitted)

일반 지역주민들에 있어서 Cd에 폭로되는 주된 경로는 소화기계이나 아직까지 소화기계에서의 Cd 흡수기전은 잘 알려져 있지 않은 편이다. 이번 연구에서는 식이를 이용하여 실험동물의 체내 Fe 수준을 조절함에 따라 Fe 이동단백질로 알려진 DMT1의 발현과 Cd 흡수와의 관련성을 관찰함으로서 금속이온의 흡수기전에 대한 이해를 높이고자 하였다. (중략)

Certain chlorinated propanols occur as contaminants in hydrolysed vegetable proteins. Processing of defatted vegetable proteins by traditional hydrochloric acid hydrolysis leads to the formation of 3-monochloro-1, 2-propanediol(3-MCPD). The objective of this study was to determine the toxicity of 3-MCPD in the rat following oral(gavage) administration for 13 weeks. (omitted)

1,3-Dichloro-2-propanol(1,3-DCP), together with 3-monochloro-propane -1,2-diol(3-MCPD), is a well-known contaminant of acid-hydrolysed vegetable protein. 1,3-DCP has also been found to occur in a range of other foods and ingredients, most notable in soy sauce. The objective of the study was to determine the toxicity of the 1,3-DCP in the rat following oral administration for 13 weeks. (omitted)

The Bupleuri Radix, called as "Siho" in Korea has been widely used in Korea, China, and Japan as Traditional Herbal Medicine since ancient times and currently. Although saikosaponins isolated from the Bupleuri Radix had metabolic and anti-inflammatory action, it's toxicity was not screened completely. Recently, many herbal medicines are imported from China but safety of these was not evaluated. (omitted) (omitted)

The reactivity and toxicity of arsenic compounds depend on the their oxidative states. Exposure to arsenic causes many human health effects, including cardiovascular, hepatic and renal disease, in addition to cancer in kidney, liver, lung, urinary bladder and skin. The cytotoxic effects of arsenite on normal hepatocyte, which most of its biotranfomation takes place. (omitted)

Epidemiological studies of arsenic have shown that chronic exposure to arsenic can result in an increased incidence of cancer of the lung, skin, bladder and liver. It is impossible that the toxicity study of arsenic in the human, we become to measure in vitro cytotoxicity of inorganic and organic arsenic in the human normal liver cells including Chang Liver and WRL. (omitted)

Aflatoxins are metabolites of fungi Aspergillus spp. that world-widely contaminate diverse foodstuffs including com and peanuts. It is well known that aflatoxins are highly mutagenic, carcinogenic and possibly teratogenic. Although aflatoxins have received the great attention among the various mycotoxins due to their potent hepatocarcinogenicity in certain species, it is extremely crucial to elucidate the relative toxicity and carcinogenicity of the types (B$_1$, B$_2$, G$_1$ and G$_2$) of aflatoxins for the risk assessment.(omitted)

Aflatoxins are produced by Aspergillus flavus, parasiticus and their related fungi that grow in improperly stored foods such as com, rice, peanuts and other cereals. In addition to its high mutagenicity and cytotoxicity, aflatoxin B$_1$ (AFB$_1$) is a potent hepatocarcinogen in experimental animals and an important factor for the human liver cancer. In spite of a high attention to the hepatocarcinogenicity of aflatoxins, the relative toxicity, for the risk assessment, of other types (AFB$_2$, AFG$_1$ and AFG$_2$) of the toxin was not fully studies.(omitted)

Effects of repeated treatment with butylated hydroxyanisole (BRA) on the induction of glutathione S-transferases (GSTs) and teratogenicity of cyclophosphamide were investigated in rats. Pregnant rats were orally treated with BRA (50 mg/kg) for 7 days, from days 6 to 12 of gestation, and subcutaneously challenged with cyclophosphamide (15 mg/kg) 2 hr after the final treatment. On day 20 of gestation, the maternal and fetal abnormalities were examined.(omitted)

A case-control study was designed to determine the possible association between dioxin like compounds (such as TCDD, PCDDs, PCDFs, and PCBs) and the occurrence and severity of endometriosis using CALUX bioassay method.(omitted)

Pomegranate, a small tree originating in Orient, belongs to Punicaceae family. The seeds contain an oil of which about 80% is rare trans 18 carbon fatty acid (punicic acid), and have highest botanical concentration of a sex steroid, estrone. Pharmacological properties of pomegranate extract have been studied, with anti-microbial, anti-parasitic, anti-viral, and anti-cancer effects. (omitted)

INTRODUCTION: Recent industrial society has widely exposed to PAHs that are coming from the incomplete combustion of organic material as widespread environmental contaminants. Biological activities of PAHs are not known although PAHs are considered as carcinogens. (omitted)

It is well known that osteoblasts and osteoc1asts playa key role in bone metabolism. They involve in osteoformation or bone destruction which are ragulated by various factors such as thyroid hormone, parathyroid hormone, estrogen, growth factor and cytokine. Recently, it is demonstrated that oxidative stress is one of pathological factors in bone metabolism, but it is left unknown about mechanism between oxidative stress and bone metabolism.(omitted)

Tributyltin (TBT) used world-wide in antifouling paints for ships is a widespread environmental pollutant and cause reproductive organs atrophy in rodents. At low doses, antiproliferative modes of action have been shown to be involved, whereas at higher doses apoptosis seems to be the mechanism of toxicity in reproductive organs by TBT. (omitted)

Dichlorodiphenyltrichloroethane (DDT), is a widespread environmental pollutant. In this study, we investigated the effect of DDT on testosterone production through aromatase and investigated its molecular mechanism in testicular leydig cell, R2C. We investigated that the effects of DDT on testosterone production and its effects on aromatase activity in R2C cell by radio immunoassay (RIA). (omitted)

Induction of glutathione S-transferases is associated with cancer chemoprevention. We reported that PD98059, an MKK1 inhibitor, induces glutathione Stransferase A2 (rGSTA2). This report comparatively examines the role of CCAAT/enhancer binding protein (C/EBP) and Nrf-2 in the induction of rGSTA2 by PD98059. PD98059 at the concentrations effective for the inhibition of MKKI increased the rGSTA2 protein and mRNA levels in H4IIE cells. (omitted)

Familial form of Alzheimer's disease (FAD) is caused by mutations in presenilin-1 and presenilin-2 (PS2). PS1 and PS2 mutation are known to similar effects on the production of amyloid $\beta$ peptide (A$\beta$) and cause of cell death in the Alzheimer's brain. The importance of the alternation of calcium homeostasis in the neuronal cell death by PS1 mutation in a variety of experimental system has been demonstrated. (omitted)

Silica has been known to be a factor in acute cell injury and chronic pulmonary fibrosis. In Rat2 fibroblasts, silica induced the activation of NFkB, which plays a crucial role in regulating the expression of many genes involved in the subsequent inflammatory response. In addition, we observed that TAK1 and NIK were involved in silica-mediated NF-kB activation in Rat2 cells. (omitted)

Oxidative stress is considered to be associated with many diseases, such as inflammatory and cardiovascular diseases, aging, and cancer. An important etiological mechanism of these diseases may be a causal relationship between the presence of oxidants and the generation of lipid hydroperoxides derived from enzymatic reactions or xenobiotic metabolism. (omitted)

We have previously shown that 2, 3' , 4, 5' -tetramethoxystilbene(TMS), a trans-stilbene analogue, is one of the most potently selective inhibitor of recombinant human cytochrome P450 1B1 in vitro. In the present studies, the effects of TMS on the expression of cytochrome P450 1B1 were investigated in human mammary cell lines such as MCF-7 and MCF-10A. (omitted)

Organophosphorus (OP) pesticides have largely replaced the use of organochlorine pesticides and have been widely used in agriculture and houses in recent years because of their rapid breakdown in water and their low environmental persistence. As a result, consumers are directly or indirectly exposed to organophosphorus pesticides through several food groups including meat, dairy products, fruits, vegetables, dried foods, and most processed food in which a significant amount of pesticide residues have been found.(omitted)

The use of skin whitening agents have been recently increased in various kinds of cosmetic products, although there were reports that whitening agents might cause allergic contact dermatitis. A murine local lymph node assay (LLNA) has been developed as an alternative to guinea pigs for contact sensitization potential. This study was carried out to investigate the skin sensitization potential of three whitening agents, kojic acid, arbutin, azelaic acid, by LLNA using a non-radioistopic endpoint.(omitted)

Recent studies suggest that inflammatory events are implicated in a variaty of human diseases such as cancer and neurodegenerative diseases, and non-steroidal anti-inflammatory drugs have beneficial effects for the treatment or prevention of these disorders. Cyclooxygenase-2 (COX-2), the rate-limiting enzyme in the prostaglandin(PG) synthesis, is induced by various pro-inflammatory stimuli including nitric oxide(NO) and has been reported to cause and/or aggravate neuronal cell death.(omitted)

Mutations of p53 tumor suppressor gene have been associated with exposure to carcinogens. Cultured human breast epithelial cells (MCF10A) were treated with Benzo(a)pyrene(BaP) or N-Methyl-N'-nitro-N-nitrosoguanidine(MNNG). MCF10A cells were grown in DMEM/F12 medium and trated for 6, 12, 24, 48 and 96h with Bap (1, 10 and 100 $\mu$M) dissolved in dimethylsulfoxide(DMSO). (omitted)

Benzoyl peroxide is a High Production Volume Chemical, which is produced about 1,375 tons/year in Korea as of 2001 survey. The substance is mainly used as initiators in polymerization, catalysts in the plastics industry, bleaching agents for flour and medication for acne vulgaris. In this study, Quantitative Structure-Activity Relationships (QSAR) is used for getting information on the physical-chemical properties of this chemical. (omitted)

국내에서 식용되고 있는 패류 내의 중금속 오염도를 검색하기 위하여 5, 6, 7, 8, 10, 12월 동안 12종, 70개의 시료를 수집하였다. 젖은 시료 약 3g에 질산과 과산화수소를 가하여 마이크로파 분해 장치로 습식분해하고 희석하여 ICP-MS, 원자흡광 광도계, 원자 형광 광도계로 분석 하였다. 분석 원소는 Hg, Pb, Cd, As를 포함하여 13종이며 계절에 따른 중금속 오염도의 변화양상을 보았다. (중략)

Various parameters of blood may be fluctuated by environmental factors such as transportation stress including diet, temperature, and so on). Thirty five 3- to 5 years-old cynomolgus monkeys were imported from Japan to evaluate potential toxic effect of a new biopharmaceutical. (omitted)

n view of the role of haptoglobin as a candidate for physical performance, we investigated the protein polymorphism of the haptoglobin in elite Korean male athletes. The serum sample was collected from 120 Korean male eliteathletes. The haptoglobin phenotypes were determined by polyacrylamide gel electrophoresis, followed by peroxidase staining. (omitted)

Extracts of Artemisia asiatica Nakai (Asteraceae) have been shown to have anti-inflammatory and anti-oxidative activities. Eupatilin (5,7-dihydroxy-3,4,6-tri-methoxy-flavone), one of the pharmacologically active ingredients derived from Artemisia asiatica, has been shown to induce apoptosis in promyelocytic leukemia (HL-60) cells. (omitted)

Oxidative stress induced by reactive oxygen intermediates (ROIs) has been implicated in a variety of human diseases including cancer, diabetes, rheumatoid arthritis and neurodegenerative disorders. Hydrogen peroxide ($H_2O$$_2$), a representative ROI which is produced during the cellular redox process, can cause cell death via apoptosis and/or necrosis depending on its concentrations. (omitted)

beta-Amyloid peptide is considered to be responsible for the formation of senile plagues that accumulate in the brains of patients with Alzheimers disease. There has been a paucity of evidence to support the involvement of reactive oxygen and/or nitrogen species (ROS and/or RNS) in beta-amyloid-induced neuronal cell death. (omitted)

Cypermethrin is one of the pyrethroids, synthetic derivatives of naturally occurring pyrethrins. Cypermethrin has been developed as an insecticide, and is now in worldwise use for control of a wide range of insects, providing potential for human exposure. Our previous study suggested estrogenic activity of cypermethrin. A chemical with hormonal activity could adversely affect reproduction and development. (omitted)

It has been known that elevated levels of COX-2 is associated with resistance to apoptosis in cancerous or transformed cells. However, recent studies have shown that up-regulation of COX-2 may be implicated in induction of apoptosis. Previous studies from this laboratory have shown that a novel alkylphospholipid type antitumor agent ET-18-O-$CH_3$ (l-O-octadecyl-2-0-methyl-glycero-3-phosphocholine) induces COX-2 expression in H-ras transformed human breast epithelial cells (MCF10A-ras) while it causes apoptosis in the same concentration range.(omitted)

Diethylhexyl phthalate (DEHP) was known as endocrine disrupter revealing reproductive / developmental toxicity. For a long time, risk due to DEHP released from PVC medical devices was became an issue for patient receiving blood bag, iv injection solution like saline and Hartman's solution. This study was conducted to suggest permissible intake level (PIL) of DEHP based on reproductive toxicity, to quantify daily intake level of DEHP can be exposed to patient through various medical treatment and to estimate risk values of DEHP released from PVC medical devices.(omitted)

The incidence of liver cancer is markedly sex-differentiated epidemiologically, with a much higher frequency in men than in women. In experimental animals, male have higher incidence of liver tumors than female in carcinogen-induced tumors as well as spontaneous ones. Our studies were investigated to examine the modifying effects of sex hormones in the proneoplastic lesions of liver on diethylnitrosamine (DEN) - induced hepatocarcinogenesis. (omitted)

Diisodecyl phthalate (DIDP) which has high physical flexibility, various colors, low viscosity, high stability is used as coating material in ballon, vinyl ink, tent, textile, home and cars interior design and electric cable. In rodents, DIDP is suspected to be a peroxisome proliferator, a nongenotoxic carcinogen. In this study, we performed the carcinogenicity test of DIDP. (omitted)

Ginger (Zingiber officinale Roscoe, Zingiberaceae) has a wide array of pharmacologic effects. Our previous studies have demonstrated that [6]-gingerol, a major pungent ingredient of ginger, inhibits mouse skin tumor promotion and anchorage-independent growth of cultured mouse epidermal cells stimulated with epidermal growth factor. In this study, we have investigated the molecular mechanisms underlying chemopreventive effects of [6]-gingerol on mouse skin carcinogenesis. Cyclooxygenase-2 (COX-2), a key enzyme in the formation of prostaglandins, has been recognized as a molecular target of many chemopreventive as well as anti-inflammatory agents. The murine COX-2 promoter contains several transcriptional elements, particularly those involved in regulating inflammatory processes. One of the essential transcription factors responsible for COX-2 induction is NF-kappa B. Topical application of [6]-gingerol inhibited the COX-2 expression through suppression of NF-kappa B activation in phorbol ester-treated mouse skin. [6]-Gingerol, through down-regulation of p38 MAPK, abrogated the DNA binding activity of NF-kappa B by blocking phosphorylation of p65/RelA at the Ser 536 residue. These findings suggest that [6]-gingerol exerts an anti-tumor promotional activity through inhibition of the p38 MAPK-NF-kappa B siganling cascade in mouse skin.

Ketoconazole is a well-studied drug that blocks fungal growth and testosterone synthesis in humans and rodents by inhibiting the activity of cytochrome P-450 enzymes. But there were no reports that ketoconazole affects on enzymes related to degradation of testosterone. Aromatase converts testosterone to estradiol. Change of aromatase protein level may destroy hormone homeostasis. (omitted)