• 동의생리병리학회지
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• 제16권1호
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• pp.78-88
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• 2002

Experimental animals were divided into 5 groups; normal, cadmium control, and 3 experimental groups. Cadmium control and experimental groups were exposed to 1 mg/㎥ of cadmium aerosol in air by inhalation exposure for 6 hours/day, 5 days/week during 4 weeks. Dosages of 20, 40, and 80mg/kg of extracts of persimmon leaves were intraperitoneally injected to experimental groups respectively and several toxicological parameters and induction of metallothionein were measured from the rats that inhaled cadmium aerosol in air. The results of this study were as follows. Cadmium concentration that cadmium control and experimental groups were inhaled was 0.980±0.061 mg/㎥. Mass median diameter of cadmium aerosol for inhalation exposure was 4.93±0.483㎛. Cadmium content of normal group in lung was 0.088㎍/g and the highest cadmium content in lung, 55.492㎍/g was from 80mg/kg dose group. Cadmium concentration of normal group in blood was 0.348㎍/100㎖ and the highest cadmium concentration in blood, 2.642㎍/100㎖ was from cadmium control. Cadmium concentration of normal group in liver was 0.010㎍/g and the highest cadmium concentration in liver, 31.100㎍/g was from 20mg/kg dose group. Cadmium concentration of normal group in kidney was 0.030㎍/g and the highest cadmium concentration in kidney, 2.526㎍/g was from cadmium control. Cadmium concentration of normal group in intestine was O.064㎍/g and the highest cadmium concentration in intestine, 0.300㎍/g was from 80mg/kg dose group. The highest cadmium concentration in urine by week was 6.080㎍/day from 20mg/kg dose group in the fouth week and the highest cadmium concentration in feces by week was 341.731㎍/day from 20mg/kg dose group in the fouth week. Metallothionein concentration of normal group in lung was 5.769㎍/g and the highest in lung, 30.986㎍/g was from 80mg/kg dose group. Metallothionein concentration of normal group in liver was 38.856㎍/g and the highest in liver, 169.378㎍/g was from 40mg/kg dose group. Metallothionein concentration of normal group in kidney was 22.228㎍/g and the highest in kidney, 47.898㎍/g was from 80mg/kg dose group. Metallothionein concentration of normal group in intestine was 2.170㎍/g and the highest in intestine, 13.642㎍/g was from 80mg dose group.

• 대한한방종양학회지
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• 제3권1호
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• pp.85-98
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• 1997

연구배경 종양은 그 발생원인과 성장기전이 자세히 밝혀져 있지 않는 질병으로 최근 사망원인의 제1원인으로 급격히 발생빈도가 증가하고 있다. 종양환자의 수는 점점 증가하는 추세이며, 그에 따른 사망자의 수도 늘고 있다. 종양을 치료하는 방법으로 수술요법 면역요법 방사선요법 화학약물요법 골수이식 호르몬요법등이 사용되어 왔으며, 최근에는 전통적인 한약재를 이용한 종양파괴 및 종양의 성장을 억제하는 약재의 연구가 활발히 시도되고 있다. 본 연구에서는 '노수토홍(勞嗽吐紅)'에 사용되는 인삼백합탕(人蔘百合湯)을 사용하여 종양파괴 및 종양의 성장억제능을 연구하고자 하였다. 연구방법 인삼백합탕을 전이암 실험에 다용(多用)되는 B16세포를 대상으로 세포독성을 MTT검사법에 의하여 실험한 후 $IC_{50}$을 측정하였다. 그 후 동물실험으로 C57BL/6에 B16세포를 주입시킨 후 고형암의 중량과 폐에 전이된 흑생종의 집락의 수를 측정하였고, 생존기간의 연장정도를 측정하였다. 연구결과 인삼백합탕 구성약물의 시험관내 세포독성을 측정하기 위하여 MTT검사법으로 측정한 결과 농도에 비례하여 생존율은 감소하였고, $IC_{50}$을 산출한 결과 백출, 홍화, 계피, 인삼등이 낮은 수치를 나타내었다. 인삼백합탕엑스의 시험관내 세포독성은 농도에 비례하여 생존율이 감소하였고, $IC_{50}$은 $0.0002437{\mu}g/ml$을 나타내었다. B16세포를C57BL/6의 복강에 주입시켜 고형종양의 무게를 측정한 결과 대조군에 비하여 유의성있는 감소를 보였다(p<0.05). B16세포를 C57BL/6의 꼬리정맥에 주입하여 폐전이암을 유발시킨 후 폐의 표면에 생긴 집락의 수를 측정한 결과 대조군에 비하여 유의성있는 감소를 보였다(p<0.001). B16세포를 C57BL/6의 꼬리정맥에 주입하여 폐전이암을 유발시킨 후 생존일수를 측정한 결과 평균치가 대조군은 23일, 투여군은 26일을 나타내어 113%의 증가를 보였다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2909-2912
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• 2012

Aim: To evaluate efficacy and tolerability of topotecan treatment for recurrent small cell lung carcinoma. Patients and Methods: A total of 62 patients were evaluated retrospectively. Statistical analysis was performed using GraphPad Instat (version 3.05). Results: DFifty five of patients (89%) were male and 7 (11%) were female. Median age was $56.7{\pm}9.3$ (34-75). Forty eight of patients (80%) were extensive stage (ES) at the time of diagnosis. Fifty of the patients (80.6 Medical Oncology Clinic) were given median 5.36 cycles of cisplatin-etoposide (2-8 cycles). Time to recurrence was $15.6{\pm}6.13$ weeks in patients with limited stage (LS) and $6.3{\pm}3.82$ weeks in extensive stage (ES) (p<0.0001). Overall survival was $14.0{\pm}6.08$ months in ES and $17.9{\pm}6.88$ months in LS. The difference between two groups was statistically meaningful (p=0.0447). The overall survival of the patients was $14.8{\pm}6.43$ months (4.5-40 months). In terms of survival, there was no difference between males and females (p=0.1171). In 17 (27%) patients who were refractory to topotecan or in whom progression occurred other chemotherapies were used. Conclusion: Small cell lung cancer is chemosensitive, but recurrences occur in short time. Other chemotherapy regimens are used in progression. Topotecan is one of them. Patients who were young and in whom recurrences occur late had given better response to topotecan. Because of the retrospective nature of the study, we couldn't reach the records exactly and consequently, rate and duration of response couldn't be calculated. In recurrent SCLC topotecan is one of the treatment choices. But both hematological and non hematological side effects should be taken into consideration.

• Toxicological Research
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• 제21권4호
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• pp.347-353
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• 2005

Eukaryotic initiation factor 4E (elF4E) is a key element for cap-dependent protein translation controlled by affinity between elF4E and 4E-binding protein 1 (4E-BP1). Rapamycin can also affect protein translation by regulating 4E-BP1 phosphorylation. Tobacco-specific nitrosamine, 4(N-methyl-N-nitrosamino )-1-(3-pyridyl)-1-butanone (NNK) is a strong lung carcinogen, but its precise lung cancer induction mechanism remains unknown. Relative roles of cap-dependent and -independent protein translation in terms of NNK-induced lung carcinogenesis were elucidated using normal human bronchial epithelial cells. NNK concentrations applied in this study did not decrease cell viability. Addition of NNK restored rapamycin-induced decrease of protein synthesis and rapamycin-induced phosphorylation of 4E-BP1, and increased expression levels of mTOR, ERK1/2, p70S6K, and Raf-1 in a concentration-dependent manner. NNK also caused perturbation of normal cell cycle progression. Taken together, NNK might cause toxicity through the combination of restoration of 4E-BP1 phosphorylation and increase of elF4E as well as mTOR protein expression, interruption of Raf1/ERK as well as the cyclin G-associated p53 network. Our data could be applied towards elucidation of the molecular basis for lung cancer treatment.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7303-7307
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• 2014

Objective: To explore the clinical efficacy of gemcitabine concomitant with nedaplatin and drug resistance in the treatment of non-small cell lung cancer (NSCLC) and associated molecular predicators. Materials and Methods: A total of 68 patients diagnosed with NSCLC by histology served as the study objects and were randomly divided into an observation group treated with gemcitabine concomitant with nedaplatin and a control group with cisplatin concomitant with gemcitabine, 34 cases for each group. Short-term and long-term efficacies, adverse responses as well as the expression of nucleotide excision repair cross complementing 1 (ERCC1), ribonucleotide reductase subunit M1 (RRM1) and lung resistance-related protein (LRP) in NSCLC tissues in both groups were assessed. Results: The short-term objective response rate (ORR) and disease control rate (DCR) were 35.3% (12/34) and 76.5% (26/34) in the observation group and 38.2% (13/34) and 85.3% (29/34) in the control group, respectively, the differences not being statistically significant. The time to progression (TTP) in both groups were 1~12 months, while the median TTP was 135 d and 144 d, respectively. Though the survival was slightly higher in the control group, there were no significant differences in TTP and survival time. The rates of decreased hemoglobin, vomiting and nausea as well as renal toxicity were evidently lower in the observation group, while other adverse responses demonstrated no significant difference. The positive expression rates of ERCC1, RRM1 and LRP were 47.1% (16/34), 61.8% (21/34) and 64.7% (22/34) in the observation group, respectively. Compared with negative ERCC1 expression, ORR had decreasing trend and the overall survival time (OS) decreased significantly in patients with positive ERCC1 expression, which were markedly decreased by the positive expressions of RRM1 and LRP. Conclusions: Gemcitabine concomitant with nedaplatin has significant effects in the treatment of NSCLC, with an adverse response rate obviously lower than for cisplatin concomitant with gemcitabine, suggesting that wider use in the clinic is warranted. Additionally, the positive expressions of ERCC1, RRM1 and LRP may increase patient drug resistance, so they can be applied as the chemotherapeutic predicators to guide individualized therapy of NSCLC patients.

• Journal of Preventive Medicine and Public Health
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• 제27권1호
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• pp.84-106
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• 1994

Hyperbaric oxygen (HBO) therapy for carbon monoxide (CO) poisoning eventually inducing the hypoxia-reoxygenation condition, may produce oxygen free radicals, which forms 8-hydroxydeoxyguanosine (8-OH-dG) by attacking C-8 position of deoxyguanosine (dG) in DNA. Effects of oxygen partial pressure or duration of HBO therapy with or without CO poisoning on the tissue 8-OH-dG formation were investigated. Male Sprague-Dawley rats were grouped and exposed to air (control group), 4000 ppm of CO for 10 to 30 minutes (CO only group), air for 30 minutes after 30 minute exposure to 4000 ppm of CO(CO-air exposure group), HBO after 30 minute exposure to 4000 ppm of CO(CO-HBO group), or HBO therapy fo. $10{\sim}120$ minutes(HBO only group). The 8-OH-4G concentrations in the brain and the lung tissues were measured with high performance liquid chromatography and electrochemical detector (ECD). Average concentrations of the 8-OH-dG of each group were statistically compared. In the brain tissues, 8-OH-dG concentrations of the CO only group, the CO-air exposure group, and the CO-HBO group did not significantly differ from those of the control group. Similar insignificance was also found between the CO-HBO group and the HBO only groups. No appreciable dose-response relationship was observed between the 8-OH-dG concentration and the oxygen partial pressure or the duration of HBO. However, the 8-OH-dG concentrations of the 30 minute CO only group were higher than those of the CO-air exposure group (p-value<0.05). In the lung tissues, there were no significant differences between the 8-OH-dG concentrations of the control group and those of the CO only group, the CO-air exposure group, and the CO-HBO group. However, mean 8-OH-dG concentration of the CO-air exposure group was significantly higher than that of the CO only group under the same CO exposure condition(p-value<0.05). With the duration of CO exposure, the 8-OH-dG concentrations of the lung tissues decreased significantly (p-value<0.05). The concentrations of 8-OH-dG in the lung tissues proportionally increased with the duration of HBO, but no such relation was observed with the oxygen partial pressure. These results suggest that the brain may be more resistant to oxygen free radicals as compared with the lungs, and that oxygen toxicity following HBO may be affected by factors other than oxygen free radicals.

• 한국환경보건학회지
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• 제47권2호
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• pp.111-122
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• 2021

Objectives: There was a judgment of acquittal for the manufacturer SK Chemical and the vendor Aekyung regarding humidifier disinfectant (HD) containing 5-chloro-2-methylisothiazol-3(2H)-one/2-methylisothiazol-3(2H)-one (CMIT/MIT). The rationale used in this judgement is discussed here in the light of scientific consideration. Methods: The sentencing document for the judgements was obtained from the Korea Supreme Court Service. In particular, the judgements made by the court related to the risk of HD and external and internal exposure to CMIT/MIT are discussed based on scientific evidence. Results: Rendering a determination in a criminal trial of insufficient evidence of causation, the court dismissed the prosecution's motion that humidifier disinfectant-associated lung injuries (HDLI) and asthma were associated with the utilization of these products. However, CMIT/MIT, a strong sensitizing and corrosive substance, has been reported to be associated with brain toxicity, allergic contact dermatitis, and asthma. Furthermore, the judgment did not consider total consumption amounts or the cumulative dose of CMIT/MIT in the humidifier. Lastly, there are several cases supporting the fact that exposure to water-soluble substances including CMIT/MIT can cause lower respiratory tract diseases. In addition to cases of asthma among the workers exposed to CMIT/MIT, we identified lung injury victims who were exposed to HDs exclusively containing CMIT/MIT. Conclusions: We conclude that there is sufficient evidence supporting the assertion that HDs containing CMIT/MIT cause lung injuries, including asthma, contrary to the court's judgement.

• 한국산학기술학회논문지
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• 제15권4호
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• pp.2189-2198
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• 2014

본 연구는 제초제 음독 중에서 가장 치명률이 높은 파라쿼트 중독의 독성 감소를 위하여 파라쿼트 독성 기전으로 알려진 파라쿼트 유도성 활성산소종을 감소시키기 위해 기존의 항산화제들 치료제와는 달리, 사전에 산소 농도를 줄여서 파라쿼트에 의한 활성 산소종 발생 자체를 줄이는 저농도 산소요법의 유용성을 연구하였다. 이를 위해 백서를 활용하여 생존률 및 파라쿼트에 의한 활성 산소종의 영향을 가장 빠르고 많이 받는 폐조직의 육안적 조직학적 변화를 비교 분석함으로써 세포 독성 상황에서 저농도 산소요법의 효과를 분석하였다. 그 결과 저농도 산소요법을 처리한 군에서 유의한 생존률 증가와 함께 H&E Stain결과에서는 염증세포 증가 및 Aveolar space에 부종 소견이 저농도 산소요법을 함께 시행한 군에서 완화된 소견을 확인할 수 있었다. 또한 파라쿼트의 독성기전의 핵심인 산화스트레스발생 분석을 시행한 결과, MDA assay, Glutathione assay 및 SOD Assay모두에서 파라쿼트는 산화스트레스를 증가하지만 파라쿼트와 함께 저농도 산소요법을 처리한 경우 산화 스트레스가 감소함을 증명하였다. 이를 통해 본 연구는 임상에서 파라쿼트 중독에 대한 새로운 치료 대안으로서의 기초 연구로서 활용이 기대된다.

• 한국환경성돌연변이발암원학회지
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• 제26권3호
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• pp.77-85
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• 2006

2,3,7,8-Tetrachlorodibenzo-$\rho$-dioxin(TCDD) displays high toxicity in animals and has been implicated in human carcinogenesis. Although TCDD is recognized as potent carcinogens, relatively little is known about their role in the tumor promotion and carcinogenesis. It is known that TCDD can increase of cancer risk from various types of tissue by a mechanism possibly involving the aryl hydrocarbon receptor (AhR) activation. In this study, effects of TCDD on cellular proliferation of normal human skin and lung fibroblasts, Detroit551 and WI38 cells were investigated. In addition, to enhance our understanding of TCDD-mediated carcinogenesis, we have investigated process in which expression of Erk1/2, cyclinD1, oncogene such as Ha-ras and c-myc, and their cognate signaling pathway. TCDD that are potent activators of AhR-mediated activity was found to induce significant increase of cytochrome P4501A1 mRNA expression, suggesting a presence of functional AhR. These results support that CYP1A1 enzyme may be involved in the generation of TCDD-induced toxicity. Moreover mitogen-activated protein kinases (MARKs) phosphorylation and cyclin D1 overexpression are induced by TCDD, which corresponded with the progression of cellular proliferation. However, TCDD did not affected Ha-ras and c-myc mRNA expression. Taken together, it seems that TCDD are could be a part of cellular proliferation in non-tumorigenic normal human cells such as Detroit551 and WI38 cells through the upregulation of MAPKs signaling pathway regulating growth of cell population. Therefore, AhR-activating TCDD could potentially contribute to tumor promotion and Detroit551 and WI38 cells have been used as a detection system of tumorigenic effects of TCDD.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2002년도 Current Trends in Toxicological Sciences
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• pp.36-42
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• 2002

Diesel exhaust (DE) has been recognized as a noxious mutagen and/or carcinogen, because its components can form DNA adducts. Mechanisms governing the susceptibility to DE and the efficiency of such DNA adduct formation require clarification. The transcription factor Nrf2 is essential for inducible and/or constitutive expression of a group of detoxification and antioxidant enzymes, and we hypothesized that the nrf2 gene knockout mouse might serve as an excellent model system for analyzing DE toxicity. To address this hypothesis, lungs from nrf2(-/-) and nrf2(+/-) mice were examined for the production of xenobiotic-DNA adducts after exposure to DE (3 $mg/m^{3}$ suspended particulate matter) for 4 weeks. Whereas the relative adduct levels (RAL) were significantly increased in the lungs of both nrf2(+/-) and nrf2(-/-) mice upon exposure to DE, the increase of RAL in the lungs from nrf2(-/-) mice exposed to DE were approximately 2.3-fold higher than that of nrf2(+/-) mite exposed to DE. In contrail, cytochrome P4501Al mRNA levels in the nrf2(-/-)mouse lungs were similar to those in the nrf2(+/-) mouse lungs even after exposure to DE, suggesting that suppressed activity of phase II drug-metabolizing enzymes is important in giving ise to the increased level of DNA adducts in the Nrf2-null mutant mouse subjected to DE. Importantly, severe hyperplasia and accumulation of the oxidative DNA adduct 8-hydroxydeoxyguanosine were observed in the bronchial epidermis of nrf(-/-) mite following DE exposure. These results demonstrate the increased susceptibility of the nrf2 germ line mutant mouse to DE exposure and indicate the nrf2 gene knockout mouse nay represent a valuable model for the assessment of respiratory DE toxicity.