• Environmental Analysis Health and Toxicology
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• v.18 no.2
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• pp.69-76
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• 2003

Effects of ambient nitrite, NO$_2$$\^$-/, at 1, 3, 10 and 30 mg/1, on the changes of plasma nitrite/nitrate and on hepatic drug - metabolizing enzyme activity were examined in the juvenile Israeli carp, Cyprinus carpio. When the fish were exposed to 1 and 3 mg/1 NO$_2$$\^$-/, there was an exposure duration-dependent increase in plasma NO$_2$$\^$-/ over the 96-hr period reaching 6∼7 fold excess the ambient concentration. In the fish exposed to 10 mg/1, a plateau concentration of less than 2-fold of the environment was attained in 12 hr. With 30 mg/1, however, the maximal plasma NO$_2$$\^$-/ was 41.25 mg/1 at 12 hr followed by a gradual decline. There was a concentration-dependent increase in methemoglobin (metHb) level in all NO$_2$$\^$-/ -exposed groups and a significant decrease in hematocrit value in 30 mg/l group after 96-hr exposure. Apart from the blunted increase in plasma NO$_2$$\^$-/ with higher NO$_2$$\^$-/ (10 and 30 mg/1) exposure, the ratio of plasma NO$_3$$\^$-/ to NO$_2$$\^$-/ was signifirantly higher in these groups compared to 1 and 3 mg/1. The imbalance in the plasma NO$_3$$\^$-//NO$_2$$\^$-/ at higher NO$_2$$\^$-/ exposure suggests a possible accelerated conversion of NO$_2$$\^$-/ to NO$_3$$\^$-/. Nitrite exposure did not affect the hepatic drug-metabolic activities in juvenile Israeli carp. All these data indicate that disposition of NO$_2$- differ depending upon exposed concentration and that metHb production may not be the exclusive toxic mechanism in carp.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3651-3657
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• 2014

Hepatocellular carcinoma (HCC) has a relatively higher incidence in many countries of Asia. Globally, HCC has a high fatality rate and short survival. Epirubicin, a doxorubicin analogue, may be administered alone or in combination with other agents to treat primary liver cancer and metastatic diseases. However, the toxic effects of epirubicin to normal tissues and cells have been one of the major obstacles to successful cancer chemotherapy. Here, we investigated the effects of epirubicin in combination with kappa-selenocarrageenan on mice with H22 implanted tumors and HepG-2 cell proliferation, immune organ index, morphology, cell cycle and related protein expressions in vivo and in vitro with sequential drug exposure. The inhibitory rate of tumor growth in vivo was calculated. Drug sensitivity was measured by MTT assay, and the King's principle was used to evaluate the interaction of drug combination. Morphological changes were observed by fluorescent microscopy. Cell cycle changes were analyzed by flow cytometry. Expression of cyclin A, Cdc25A and Cdk2 were detected by Western blotting. In vivo results demonstrated that the inhibitory rate of EPI combined with KSC was higher than that of KSC or EPI alone, and the Q value indicated an additive effect. In addition, KSC could significantly raise the thymus and spleen indices of mice with H22 implanted tumors. In the drug sensitivity assay in vitro, exposure to KSC and EPI simultaneously was more effective than exposure sequentially in HepG-2 cells, while exposure to KSC prior to EPI was more effective than exposure to EPI prior to KSC. Q values showed an additive effect in the simultaneous group and antagonistic effects in the sequential groups. Morphological analysis showed similar results to the drug sensitivity assay. Cell cycle analysis revealed that exposure to KSC or EPI alone arrested the cells in S phase in HepG-2 cells, exposure to KSC and EPI simultaneously caused accumulation in the S phase, an effect caused by either KSC or EPI. Expression of cyclin A, Cdc25A and Cdk2 protein was down-regulated following exposure to KSC and EPI alone or in combination, exposure to KSC and EPI simultaneously resulting in the lowest values. Taken together, our findings suggest that KSC in combination with EPI might have potential as a new therapeutic regimen against HCC.

• Toxicological Research
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• v.33 no.1
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• pp.43-48
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• 2017

With ultraviolet and visible light exposure, some pharmaceutical substances applied systemically or topically may cause phototoxic skin irritation. The major factor in phototoxicity is the generation of reactive oxygen species (ROS) such as singlet oxygen and superoxide anion that cause oxidative damage to DNA, lipids and proteins. Thus, measuring the generation of ROS can predict the phototoxic potential of a given substance indirectly. For this reason, a standard ROS assay (ROS assay) was developed and validated and provides an alternative method for phototoxicity evaluation. However, negative substances are over-predicted by the assay. Except for ultraviolet A (UVA), other UV ranges are not a major factor in causing phototoxicity and may lead to incorrect labeling of some non-phototoxic substances as being phototoxic in the ROS assay when using a solar simulator. A UVA stimulator is also widely used to evaluate phototoxicity in various test substances. Consequently, we identified the applicability of a UVA simulator to the ROS assay for photoreactivity. In this study, we tested 60 pharmaceutical substances including 50 phototoxins and 10 non-phototoxins to predict their phototoxic potential via the ROS assay with a UVA simulator. Following the ROS protocol, all test substances were dissolved in dimethyl sulfoxide or sodium phosphate buffer. The final concentration of the test solutions in the reaction mixture was 20 to $200{\mu}M$. The exposure was with $2.0{\sim}2.2mW/cm^2$ irradiance and optimization for a relevant dose of UVA was performed. The generation of ROS was compared before and after UVA exposure and was measured by a microplate spectrophotometer. Sensitivity and specificity values were 85.7% and 100.0% respectively, and the accuracy was 88.1%. From this analysis, the ROS assay with a UVA simulator is suitable for testing the photoreactivity and estimating the phototoxic potential of various test pharmaceutical substances.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.11b
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• pp.167-167
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• 2002

Many pesticides possess hormonal activity and have been thus classified as endocrine disruptors. Permethrin, a pyrethroid insecticide has little been characterized to it's hormonal potential. In the present study, effects of neonatal exposure to permethrin on the sex steroid receptor levels and hoxa-10 expression of the uteri were investigated in female mice.(omitted)

• Bulletin of the Korean Chemical Society
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• v.34 no.4
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• pp.1131-1136
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• 2013

Parabens, the esters of p-hydroxybenzoic acid, have been widely used as antimicrobial preservatives in cosmetic products, drugs, and processed foods and beverages. However, some parabens have been shown to have weak estrogenic effects through in vivo and in vitro studies. Because such widespread use has raised concerns about the potential human health risks associated with exposure to parabens, we developed a simultaneous analytical method to quantify 4 parabens (methyl, ethyl, propyl, and butyl) in human urine, by using solid-phase extraction and high-performance liquid chromatography coupled with triple quadrupole mass spectrometry. This method showed good specificity, linearity ($R^2$ > 0.999), accuracy (92.2-112.4%), precision (0.9-9.6%, CV), and recovery (95.7-102.0%). The LOQs for the 4 parabens were 1.0, 0.5, 0.2, and 0.5 ng/mL, respectively. This method could be used for quick and accurate analysis of a large number of human samples in epidemiological studies to assess the prevalence of human exposure to parabens.

• Proceedings of the Korean Society of Veterinary Pathology Conference
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• 2000.09a
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• pp.26-26
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• 2000

The consumption of cruciferous vegetables such as cabbage and broccoli have been shown to have a chemopreventive effect in human and in experimental animals. Indole-3-carbinol (I3C), one component of cruciferous vegetables, has been shown to exert its chemopreventive effect in liver, colon and mammary tissue before or concurrent exposure of carcinogen, but in some reports, there have been several evidence that consumption of I3C after carcinogen treatment induced tumor promotion in some tissues. There have been no reports about the effect of I3C after carcinogen exposure in N-Nitroso-N-methylurea (MNU)-induced mammary tumor model of rats. (omitted)

• Biotechnology and Bioprocess Engineering:BBE
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• v.9 no.4
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• pp.261-266
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• 2004

Hyperthermia (HT) in combination with anticancer drugs (ACDs) had proven to more efficacious in various cancers, although efficacies vary according to chemotherapeutic compounds and cancer types. Presently there are few data that compares anticancer efficacies among ACDs under hyperthermic conditions. Therefore, we selected three commonly used ACDs (quercetin, verapamil and doxorubicin) and compared their antitumor effects when each was treated with 43$^{\circ}C$ HT exposure. Firstly, FM3A, a murine breast cancer cell line, was treated with each ACD for 1 h followed by 43$^{\circ}C$ exposure for additional 1 h, and examined the effects of: 1) each drug, 2) 43$^{\circ}C$ HT exposure, and 3) the combination of each drug and 43$^{\circ}C$ HT exposure for 1, 6 and 24 h. The determined overall effects on FM3A cells were arrested cell proliferation, clonogenic efficiency and apoptosis. Pre-treatment of FM3A cells to each ACD followed by 43$^{\circ}C$ HT exposure produced greater antitumor effects including suppressed cell proliferation, reduced clonogenic efficiency and increased apoptotic cell death, compared to ACD treatment or HT exposure alone. Apoptotic cell death occurred in a time-dependent manner. Among the ACDs, antitumor efficacies varied in the order of doxorubicin > verapamil > quercetin. It was concluded that heat exposure during ACD treatment of caner cells may be an important factor to get a better antitumor benefit, even though this benefit may differ from one drug to another.

• Journal of Food Hygiene and Safety
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• v.36 no.3
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• pp.213-219
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• 2021

Hazardous substances are formed during food manufacturing, processing, or cooking, and may pose a threat to food safety. Here, we present a dietary exposure assessment of Korean consumer's intake of hazardous materials through a Total Diet Study (TDS) which was conducted by the Ministry of Food and Drug Safety (MFDS). The levels of exposure to materials such as acrylamide, furan, biogenic amines, etc., were estimated and risk assessments were then performed. Acrylamide and furan were selected as hazards with high priority of reduction control due to their having a margin of exposure (MOE) lower than 10,000. Risk assessment of exposure to ethyl carbamate, benzene and 3-MCPD showed MOEs higher than 100,000, indicating "safe". Dietary exposure to polycyclic aromatic hydrocarbons and benzopyrene was also found to be safe MOE levels >10,000. In addition, the results indicated safe MOEs (>1,000,000) for heterocyclic amines, nitrosamines, and biogenic amines. Most of the potential food contaminants were being kept at safe levels, however, it is necessary to continue to monitor and control exposure levels in accordance with the 'as low as reasonably achievable' (ALARA) principle.

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.10b
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• pp.112-112
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• 2003

Air pollution is made up by complex mixture exhausted from cars, industries and incinerators etc. Those pollutants come from everywhere without border and contain phototoxic and photogenotoxic chemicals including PAHs exhausted in the air. We have published that the chemicals which show phototoxicity and photogenotoxicity are closely related in mechanistic and the PAHs react as a strong photocatalyzer by radical productions under UV exposure.(omitted)

• Archives of Pharmacal Research
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• v.25 no.5
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• pp.718-723
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• 2002

CKD-602 (7-[2-(N-isopropylamino)ethyl]-(20S)-camptothecin) is a recently-developed synthetic camptothecin analogue and currently under clinical development by Chong Kun Dang Pharm (Seoul, Korea). CKD-602 showed potent topoisomerase inhibitory activity in vitro and broad antitumor activity against various human tumor cells in vitro and in vivo in animal models. This study describes the pharmacodynamics of the immediate and delayed cytotoxicity induced by CKD-602 in a human colorectal adenocarcinoma cell line, HT-29, and its intracellular drug accumulation by HPLC. The present study was designed to address whether the higher activity of CKD-602 with prolonged exposure is due to delayed exhibition of cytotoxicity and/or an accumulation of anti proliferative effect on continuous drug exposure. The drug uptake study was performed to determine whether the delayed cytotoxicity is due to a slow drug accumulation in cells. CKD-602 produced a cytotoxicity that was exhibited immediately after treatment (immediate effect) and after treatment had been terminated (delayed effect). Both the immediate and delayed effects of CKD-602 showed a time dependent decrease in 4IC_{50}$ values. Drug uptake was biphasic and the second equilibrium level was obtained as early as at 24hr, indicating that the cumulative and delayed antitumor effects of CKD-602 were not due to slow drug uptake. On the other hand, CKD-602 treatment was sufficient to induce delayed cytotoxicity after 4hr, however, longer treatment (＞24hr) enhanced its cytotoxicity due to the intracellular accumulation of the drug, which requires 24hr to reach maximum equilibrium concentration. In addition, $C^n$$\times$T=h analysis (n=0.481) indicated that increased exposure times may contribute more to the overall antitumor activity of CKD-602 than drug concentration. Additional studies to determine the details of the intracellular uptake kinetics (e.g., concentration dependency and retention studies) are needed in order to identify the optimal treatment schedules for the successful clinical development of CKD-602.