• 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.

• 한국환경성돌연변이발암원학회지
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• 제9권1호
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• pp.47-55
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• 1989

Quantitative analyses were made of pepsinogen 1 (Pg 1) decreased pyloric glands after treating male Wistar rats with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and NaCl and then with various test chemicals. Animals received MNNG in drinking water (100ng/ml) and 10% NaCl in diet for 8 weeks (group1), followed by basal diet containing 0.01% capsaicin, 0.5% allyl sulfide, 0.5% indole-3-carbinol and 0.05% germanium until 20 weeks (groups 2-5).

• 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.

• 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.

• 한국균학회지
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• 제21권3호
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• pp.230-234
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• 1993

R. nigricans Ehrenberg의 돌연변이주를 분리하기 위하여 화학적인 돌연변이원인 N-Methyl-N'-Nitro-N-Nitrosoguanidine(MNNG)과 Ethyl Methane Sulphonate(EMS)의 최적 처리 조건을 조사하였을 때, MNNG농도는 $125{\mu}g/ml$, 처리시간이 60분일 때 돌연변이율이 가장 높은 생존율 0.1-1.0%를 나타내었다. MNNG를 이용하여 영양요구성 돌연변이주 Leucine auxotroph를 분리하였으며, 포자낭병의 길이가 축소된 것, 포자낭병의 모양이 나선형으로 변한 것, 그리고 포자낭과 포자낭포자의 크기가 감소된 것 등 세 가지 형태적 변이주를 분리하였다.

• 약학회지
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• 제37권5호
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• pp.483-489
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• 1993

Bifidobacterium bifidum, one strain of medical preparations being on the market for human intestinal disorder, is very sensitive to rifampicin. If this preparation is taken with rifampicin, its therapeutic effect can't be expected. To develope rifampicin resistant mutants, B. bifidum was treated with N-methyl-N'-nitro-N-nitrosoguanidine(MNNG). All of thirty strains grown on the plates containing 10 $\mu\textrm{g}$/ml rifampicin were over 1, 000 times more resistant to rifampicin than parental strain and they were identified as B. bifidum by fructose-6-phosphoate phosphoketolase test. Three strains out of thirty, which produced almost same amount of organic acid as parental strain, were selected for further studies. They showed identical growth inhibition activity aganist E. coli compared with that of parental strain. And rifampicin was not inactivated.

• 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)

• 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.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1993년도 제2회 신약개발 연구발표회 초록집
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• pp.99-99
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• 1993

본 연구에서는 이미 benzo(a)pyrene유도 소핵시험에서 뚜렷하게 소핵생성억제능을 보인 polyhydroxy flavonol유도체중의 하나인 Galangin에 대하여 C57BL/6 mice를 이용하여 N-methyl-N'-nitro-N-nitrosoguanidine(이하 MNNG)에 의해 유도된 소핵생성빈도에 미치는 영향을 살펴보고, spleen lymphocyte 배양을 통해 bleomycin 및 MNNG유도 염색체이상에 미치는 영향과 MNNG에 의해 유발된 DNA adduts중 biomarker로서 7-methylguanine형성에 대한 Galangin의 영향을 살펴봄으로서 ,Galangin의 유전독성 억제효과 및 작용기전에 대한 연구를 하고자하며 향후 Galangin을 모핵으로하는 cancer chemopreventive agent로의 유도체 합성에 기여하고자 한다.

• 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)