• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 춘계학술대회 논문집
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• pp.83-83
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• 2003

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)

• Biomolecules & Therapeutics
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• 제1권1호
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• pp.26-30
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• 1993

Strain of treptomyces minoensis DMCJ-144 was tried to be improved so that it produces much more the $\alpha$-amylase inhibitor. Streptomyces minoensis DMCJ-144 was treated with 1 mg/mι (pH 9.0) of N-methyl-N'-nitro-N-nitrosoguanidine at $30^{\circ}C$ for 60 min and irradiated with UV light distanced 30 cm for 20 min. After mutagenesis, surviving colonies were cultured on the CM contaning acriflavine ($10{\mu}g/ml$) three times in order to enhance the mutability. And then through multi-level screening, colonies that ${\alpha}$-amylase inhibitor productibility. was Improved were selected by modified-blue value method. After third acriflavine treatment, $\alpha$-amylase inhibitory activities of selected colonies were found to be much better as compared with that of parent strain. One mutant strain showed 5.4 time inhibitory activity than the parent strain.

• Biomolecules & Therapeutics
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• 제1권2호
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• pp.183-187
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• 1993

The anticlastogenic effect of galangin, flavonoid derivative, was studied in vivo micronucleus test using C57BL/6 mice. The frequencies of micronuclei induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in bone-marrow cells of C57BL/6 mice were significantly decreased by the simultaneous treatment or multiple pre-treatment of galangin. When galangin was orally administered at 0, 0.1, 1.0, or 10.0 mg/kg twice with 24 hr interval, together with intraperitoneally administered MNNG, there were suppressive effects in the tested doses. The most marked suppressive effect was observed in the treatment group of 1.0 mg/kg (64.5%), not in the treatment group of 10.0 mg/kg (36.3%). When galangin was multiply administered at 1/7 or 1 mg/kg for 7 days respectively, galangin showed higher suppressive effect in the treatment group of 1/7 mg/kg (23.5%) rather than in the treatment group of 1 mg/kg (13.5%). In another experiment, galangin was administered at 0.001, 0.01 or 0.1 mg/kg for 1 month respectively. The suppressive effects in one month treatment gradually increased with dose-dependent manner, although suppressive effects were not high. The results showed that galangin was effective in suppressing the frequencies of micronuclei induced by MNNG. Our study indicates that galangin is a potent anticlastogenic agent against MNNG.

• Biomolecules & Therapeutics
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• 제1권2호
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• pp.137-142
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• 1993

The possible tumor-promoting activities of sodium chloride (NaCl) and dimethyl itaconate (DMI), one of the quinone reductase inducers, were examined on stomach of male Wistar rats treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Administrations of NaCl and DMI after the initiation by MNNG resulted in various sized masses in the rat forestomach. Histopathologic studies showed that the combination of NaCl and DMI made an enhancing effect on the MNNG-induced carcinogenesis, resulting in papilloma in 5 weeks and squamous cell carcinoma in 20 weeks in submucosal area of forestomach. We also used an in vivo shortterm method for evaluating possible tumor-promoting activity with ornithine decarboxylase (ODC) as a marker. The markable inductions of the ODC activities by MNNG, NaCl, and DMI were found in the pyloric mucosa of rat stomach in time-dependent manners. A single administration of MNNG induced ODC activity up to 288 pmol $CO_2$/hr/mg protein at 24 hr after the administration. NaCl caused induction of ODC with a maximum of 179 pmol $CO_2$/hr/mg protein at 8 hr after the administration. ODC was induced up to 539 pmol $CO_2$/hr/mg protein at 16 hr after the administration of DMI. Additional treatment of NaCl and NaCl plus DMl caused 2 fold and 7 fold increases, respectively, in the ODC activity of the MNNG-alone group at 24 hr after the administration. These results suggest that NaCl and DMI have promoting activities in the rat gastric carcinogenesis initiated by MNNG.

• Toxicological Research
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• 제19권2호
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• pp.91-98
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• 2003

Alkylating agents form alkylated base adducts in the DNA and cause DNA lesions leading to cell killing. In this study, we investigated the mechanism of apoptosis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in PC-3 and DU145 human prostate carcinoma cell lines. MNNG treatment resulted in the inhibition of cell proliferation in a concentration-dependent manner to a similar extent in both cell lines. This anti-proliferative effect of PC-3 and DU145 cells by MNNG was associated with morphological changed such as membrane shrinking, cell rounding up and formation of apoptotic bodies. MNNG treatment also induced a proteolytic cleavage of specific target proteins such as poly(ADP-ribose) polymerase (PARP) and $\beta$-catenin proteins in DU145 cells but in PC-3 cells. Furthermore, we observed an increase of proapoptotic protein Bax family expression and a decrease of antiapoptotic protein Bcl-2 family by MNNG treatment in a concentration-dependent manner MNNG also induced a proteolytic activation of caspase-3 and -9, which is believed to play a central role in the apoptotic signaling pathway.

• 대한수의학회지
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• 제35권4호
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• pp.793-807
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• 1995

This study was carried out to investigate the effects of diethyl maleate(DEM) on the carcinogenesis of forestomach and pyloric glandular stomach in rats caused by N-methyl-N'-nitro-N-nitrosoguanidine(MNNG). A total of 60 male 6-week-old Wistar rats were given twice intragastric injection of MMNG(200mg/kg BW), then were given diets containing 5% NaCl for 3 weeks until 4th week of the experiment. And then the animals of groups of 1 and 2 were placed on diets containing 0.2% DEM for 16 weeks until the end of 20 weeks of the experiment. On the other hand, the animals of groups of 3 and 4 were placed on basal diets for the same periods. The tissues of forestomach and liver of each group were frozen in liquid nitrogen and the activities of quinone reductase(QR) were determined by measurement of the dicoumarol-sensitive reduction of dichloro-indophenol by NADPH at 600nm. All rats were sacrificed at the end of 20 weeks of the experiment. Every animal was fasted for 24 hrs prior to sacrifice. The forestomach was fixed in 10% neutral phosphate buffered formalin for histology and the pyloric gland was fixed in sublimated formalin for immunohistochemistry of pepsinogen 1 altered pyloric gland(PAPG). The final body weight of the group given MNNG and treated with 5% NaCI and DEM was significantly decreased compared with that of the group 4(p<0.05). Food and water consumption rates were not significantly changed. The preneoplastic and neoplastic lesions of the forestomach given MNNG and treated with 5% NaCI and DEM were significantly increased compared to those of the group 4(p<0.0l). The incidence of PAPG in the groups treated with 0.2% DEM was significantly increased compared with that of the group 4(group 1:p<0.01, group 2:p<0.05). The activities of QR of forestomach in the groups treated with 0.2% DEM were significanitly increased compared with those of the group 4(p<0.001), but those of liver were not significant. These results indicate that DEM exert the enhancing effect of forestomach and glandular stomach carcinogenesis in rats pretreated with MNNG and NaCl.

• 한국식품위생안전성학회지
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• 제6권1호
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• pp.27-40
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• 1991

랫드에서 속박 및 침수 스트레스에 의한 위궤양이 MNNG(N-methyl-N'-nitro-N-nitrosoguanidine)의 위발암과정에 어떠한 영향이 있는지 알아보기 위하여 본 실험을 실시 하였다. 1 군은 시험시작 8시간 전에 스트레스를 가한 후 MNNG를 투여하였으며, 2군은 MNNG를 음수 투여한 후 MNNG에 의한 위발암 기간 중 촉진기간이라고 알려진 3~12주 사이에 매주 발암 물질과 함께 스트레스를 1회 가하였다. 3군은 양성 대조군으로서 MNNG만을 투여하였고, 4군은 음성 대조군으로 발암제를 처치하지 않았다. 전군 공히 20주에 부검하여 acidine-biotin peroxidase complex(ABC) 방법으로 면역조직 화학적 염색을 한 수 PAPG({Pepsinogen isozyme 1 Altered Pyloric Gland)에 대한 통계 분석을 하였으며, 각 군간의 체중 변화와 병리 변화를 비교하여 다음과 같은 결과를 얻었다. 1. 발암 물질을 투여한 1·2·3군이 비투여군(4군)에 비해 증체율이 유의성있게 감소하였다. (p<0.05), 그러나 발암 물질 투여군간의 체중변화에는 유의성이 없었다. 2. MNNG 투여와 함께 스트레스를 가한 군이 스트레스를 가하지 않고 MNNG만을 투여한 군에 비하여 Pg 1 변이 유문선(PAPG)의 수가 유의성 있게 증가되었다. (p<0.01). 3. 위발암 과정 중 촉진기간에 스트레스를 가한 군이 스트레스를 가하지 않고 MNNG만을 투여한 군에 비해 점막 과형성(mucosal hyperplasia) 발생이 유의성있게 증가되었다. (P<0.05)

• 한국식품과학회지
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• 제32권2호
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• pp.417-423
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• 2000

김치에서 분리한 Lactobacillus plantarum KLAB21 균주에 있어서 MNNG와 NQO에 대한 항돌연변이원성 물질 생산을 위한 최적 조건을 조사하였다. 탄소원으로 glucose를 첨가시 가장 높은 항돌연변이 효과를 나타내었으며, 질소원으로서는 yeast extract와 bactopeptone첨가시 항돌연변이 효과가 우수하였다. 탄소원으로 glucose의 농도를 2% 첨가시 MNNG와 NQO에 대한 항돌연변이 효과가 가장 우수하였으며, 질소원으로서 yeast extract는 1%와 bactopeptone의 농도는 MNNG인 경우 1%, NQO인 경우 1.5%에서 가장 우수한 항돌연변이 효과를 나타내었다. 항돌연변이원성 물질 생산을 위한 최적 배양 조건은 초기 pH, 배양 온도, 배양 속도가 각각 7.0, $37^{\circ}C$ 및 150 rpm이었다. 상기의 최적 조건에서 36시간 배양시 가장 높은 항돌연변이 효과를 나타내었는데 S. typhimurium TA100과 TA98을 이용한 경우 항돌연변이 효과가 각각 98.4%와 57.3%이었다.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Dietary and Medicinal Antimutgens and Anticarcinogens
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• pp.98-98
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• 2001

Antimutagenic effect of red pepper powder (RPP) produced in Korea depending on the varieties and producing districts were studied against Ν-methyl-Ν'-nitro-Ν-nitrosoguanidine (MNNG) in Ames test and SOS chromotest. The antimutagenic activities of green pepper, red pepper and different parts of dried red pepper were also evaluated in the same experimental systems.(omitted)

• 미생물학회지
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• 제33권3호
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• pp.199-202
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• 1997

방선균(Streptomyces) 포자와 효모(Saccharomyces) 반수체 및 배수체 세포를 대상으로 전기충격(AC 38V/1.3 cm)이 화학적 돌연변이원인 N-methyl-N'-nitro-N-nitrosoguanidine(NTG)의 세포치사효과와 돌연변이 유발에 미치는 영향을 조사하였다. 방선균의 경우 전기충격 단독 처리로는 180분 처리하였을 때 생존율이 100%이었으나 960분 처리한 경우에는 모두 사멸하였다. 전기충격과 NTG처리를 병행한 바 방성균의 경우 180분 처리시, NTG 단독 처리시보다 생존율이 72%에서 48%로 감소되었고, 반수체 효모의 경우 40분 처리시 8%에서 3%로, 배수체 효모의 경우 25%에서 10%로 각각 감소되었다. 전기충격과 NTG에 의한 영양요구 돌연변이 형성율에 있어서는 전기충격이 NTG에 의한 돌연변이율을 120분 처리 후 1.8%에서, 13.6%로, 반수체효모의 경우 40분 처리후 2.4%에서 4.8%로 각각 증가시켰다.