• The Journal of Natural Sciences
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• v.9 no.1
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• pp.45-52
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• 1997

We have examined the effects of low concentrations of MNNG, alkylating agent, in survival and mutagenesis in Aspergillus nidulans. Pretreatments of cells with nontoxic and submutagenic doses of MNNG did not reduce the cytotoxic and mutagenic effects of exposure to a high concentration of drug. The results imply that adaptive responses on survival and mutagenesis for MNNG treatments do not occur in Aspergillus nidulans. In the first mitotic cell cycle during germination, the sensitivity to MNNG has been investigated at hourly time interval, and compared with that for UV irradiation. In both UV and MNNG treatments, the sensitivity increased till S cell stage, and decreased while DNA replication continued. Different from that show for UV irradiation, lethality to MNNG reached to the maximum at G2 cell stage.

• The Korean Journal of Zoology
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• v.23 no.3
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• pp.115-123
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• 1980

The rates of escision repair at various doses and times after MNNG treatment in CHO cells were compared with the frequencies of chromosome aberrations to determine a possible relation between there two types of biological phenomena, and the results obtained were as follows: 1. the MNNG-induced excision repair was dose-dependent in te ranges between $0.5 \\times 10^-5$M. The maximum rate of excision repair was occurred in the cells soon after the treatment. The rates were then gradually decreased and appeared about 66% of 0 hour at 24 hours. 2. The rates of chromosome aberrations induced by MNNG was the highest at 6 hours, in which majority were chromatid deletions. The rates of chromatid deletions decreased, whereas chromatid exchanges increased with time, resulting is about equal rates at 24 hours after treatment. 3. The rates of excision repair at different times after MNNG treatment were roughly related to the total breaks per cell. The rates, however, did not show any relation to either chromatid exchanges or deletions. These results may suggest that excision repair may not be directly related to chromosome aberrations in MNNG treated CHO cells.

• Journal of Life Science
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• v.19 no.1
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• pp.1-8
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• 2009

In this paper, to elucidate the further mechanisms of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced growth arrest, we investigated the effect of MNNG on cell cycle and proliferation in U937 cells, a p53-null human myeloid leukemia cell line. It was found that MNNG causes an arrest at the G2/M phase of the cell cycle and induces apoptosis, which is closely correlated to inhibition of cyclin B1 and cyelin-dependent kinase (Cdk) 2-associated kinase activities. MNNG treatment in. creased protein and mRNA levels of the Cdk inhibitor p21(WAF1/CIP1), and activated the reporter construct of a p21 promoter. By using p21 promoter deletion constructs, the MNNG-responsive element was mapped to a region between 113 and 61 relative to the transcription start site. These data indicate that in U937 cells MNNG can circumvent the loss of wild-type p53 function and induce critical downstream regulatory events leading to transcriptional activation of p21. Present results indicate that the p53-independent up-regulation of p21 by MNNG is likely responsible for the inhibition of cyclin/Cdk complex kinase activity rather than the down-regulation of cyclins and Cdks expression. These novel phenomena have not been previously described and provide important new insights into the possible biological effects of MNNG.

• Journal of Nutrition and Health
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• v.29 no.7
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• pp.821-829
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• 1996

Gastric cancer was inducedd by N-nethyl-N'-nitro-N-nitrosoguanidine(MNNG) in Fisher 344 male rats. Freeze dried typical Koran feeds, aged kimchi, soybean paste and maejoo, and partially scorched barbecued bulgokee were fed to the rat in the diet, which were composing 10% of the total diet. Experimental desing was as follows ; (1) group C : Control, (2) group M : MNNG with control diet, (3) group MK : MNNG with 10% of kimchi, (4) group MS : MNNG with 10% of soybean paste and maejoo, (5) group MB : MNNG with 10% of barbecued bulagokee, (6) group MKSB ; MNNG with 10% of the mixture of kimchi, soybean paste and maejoo, and barbecued bulgokee. Each group was fed with isocaloric diet for 26 weeks. Comparing to control, the growth rate of the experimental group was decreased after administration of MNNG and experimental diet. The mortality rate of group MB was increased by 17% than the control group along with a significant decrease of body weight. The protein efficiency ratio and the food efficiency ratio of group MB were lower than the control. The incidence of gastric cancer in rats fed kimchi and barbecued bulgokee were 73% and 75%, respectively, while that of group M which fed MNNG remained only 56%. On the contrary, soybean paste and maejoo showed an inhibitory effect on the burden of gastric tumor. However, the combination of kimchi, soybean paste and maejoo, and barbecued bulogokee showed a synergistic effect of increasing tumorigenesis in rats. Pathological observations of the rat stomach represent that squamous cell type tumors occupied in most frequencies.

• Journal of Food Hygiene and Safety
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• v.6 no.1
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• pp.27-40
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• 1991

;ABSTRACT-The effects of gastric ulcer induced by restraint and water-immersion stress on gastric carcinogenesis in Wistar male rats treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were examined. Rats of group 1 were 2iven stress for 8 hours before they were received MNNG (100 mg/l) in drinking water for 20 weeks. Rats of group 2 were received MNNG first for 2 weeks and then were given stress once a week from 3rd to 12th weeks, with simultaneous MNNG adminitration and followed by MNNG only until 20th weeks. Rats of group 3 were received MNNG only as a positive control and rats of group 4 were not treated with carcinogen. All groups were sacrificed in 20 weeks. Sections of the pyloric mucosa were stained by avidin-biotin peroxidase complex (ABC) immuno-histochemical method. PAPG (pepsinogen isozyme 1 altered pyloric gland), body weight change, gross lesions and histopathological changes were examined. The results obtained from these studies were summarized as follows: 1. The mean body weight gains of the rats fed with carcinogens (group 1, 2, 3) were significantly lower than that of group 4 (control group, without carcinogen. p<0.05). However, the differences of the mean body weight of rats treated with carcinogen were not significant. 2. Stress treatment (group 1 and 2) increased the appearance of the numbers of PAPG (Pepsinogen 1 Altered Pyloric Gland) induced by carcinogen significantly compared with that of group 3 (carcinogen only, p<0.01). 3. The incidence rate of mucosal hyperplasia in pylorus was significantly increased in group 2 compared with group 3 (p<0.05).0.05).

• The Korean Journal of Zoology
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• v.19 no.4
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• pp.179-186
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• 1976

DNA repari synthesis and chromosome aberrations induced by various concentrations of alkylating agents (MMS, MNNG, MMC) in cultured human lymphocytes and HeLa $S_3$ cells were studied to determine the possibility of correlation between these two types of biological phenomena, and the results obtained were as follows: DNA repair synthesis was detected in MMC, MNNG and MMS treated HeLa $S_3$ cells at the concentrations of $3 \\times 10^{-7}M, 1 \\times 10^{-6}M, 5 \\times 10^{-4}M$, respectively. These results indicate that MMC is the most potent mutagen followed by MNNG, and MMS is the least potent among these three types of alkylating agents. MMC and MNNG did not show any significant increases of DNA repair synthesis as dose increased, while MMS did. Chromosome aberrations induced by MMC in human lymphocytes was increased as dose increased, but not chromosome exchanges. MNNG did not induce any significant amount of chromosome aberrations with doses, and exchanges were not observed in MNNG treated cells. MMS, however, induced both chromosome aberrations and exchanges, and their rates were increased as dose increased. These results suggest that DNA repair synthesis induced by these alklating agents may not be directly related to the production of chromosome aberrations and exchanges.

• Korean journal of food and cookery science
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• v.14 no.4
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• pp.333-338
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• 1998

On the mutagenicity induced by 2-aminofluorene (2-AF) with S9 mix and N-Methyl-N＇-Nitro-N-Nitrosoguanidine (MNNG) without S9 mix, the antimutagenic effects of dietary fiber (total dietary fiber, u-cellulose and pectin) from Yam were examined by the Ames assay using Salmonella typhimurium TA98 and TA100. Total dietary fiber, $\alpha$-cellulose ind pectin from natural and cultural Yam didn＇t have mutagenicity. Most of sample dietary fiber showed the antimutagenicity. Total dietary fiber from cultural Yam was more effective than that from natural Yam on mutagenicity induced by 2-AF and MNNG. $\alpha$-cellulose from cultural Yam was more effective than that from natural Yam on mutagenicity caused by 2-AF and MNNG. Pectin from natural and cultural Yam had antimutagenic effect on mutagenicity induced by MNNG. In this study, antimutagenicity on MNNG was more effective than that on 2-AF. Antimutagenic effect of Samples had influence on incubation time. $\alpha$-cellulose and pectin from natural and cultural Yam showed stronger antimutagenic effect than standard $\alpha$-cellulose and standard pectin, respectively, on mutagenicity induced by 2-AF and MNNG.

• Archives of Pharmacal Research
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• v.16 no.3
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• pp.196-204
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• 1993

Flavonol derivatives were tested for their anticlastogenic effect against induction of micronuclei by n-methyl-n'-nitor-n-nitorsoguanidine(MNNG), and against induction of chromosome aberration by bleomycin or MNNG.belomycin. For micronudeus assay, each flavonol derivative (0, 0.001, 0.01, 0.1, 1, 10 and 100 mg/kg) was administered orally twice with 24 h interval, together with intraperitioneally administered MNNG(150 mg/kg). The result showed that msot flavonol derivatives tested were effective in suppresing the frequencies of micronude induced by MNNG. For chromosome aberration assy, each flavonol derivative (0, 0.1, 1, 10m and 100 mg/kg)was administered to mice orally in vivo, and then mice were sacrificed and spleen lymphocyte cultures were made. Bleomycin $(3\;\mu$g/ml) was treated to the mouse spleen hymphocyte cultures at 24 h after con A initiation. There wre nomarked decrease tendencies in chromosome aberration unless all doses of galangin and some doses of several flavonol derivatives tested. In the another experiment, we have evaluated the effect of flavonol derivatives on the enhancement of bleomycin-induced chromsome aberration by MNNG. Most of flavonol derivtives reduced the incidence of chromosome aberration induced by in vitro treatment of bleomycin followed by in vivo treatment of MNNG. Galangin particulary showed a dose-dependent decrease tendency. Other flavonol derivative showed slightly suggest that most of flavonol derivatives may be capable of protecting the inhibition of suggest that most of flavonol derivatives may be capable of protecting the inhibition of DNA-repair by MNNG. Our data indicate clearly that flavonol derivatives can suppress MNNG-induced genotoxicity such as an induction of MNPCEs. Therfore, our results could suggest that flavonol derivtives may be useful as a chemopreventive agent of MNNG.

• Journal of Food Hygiene and Safety
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• v.24 no.1
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• pp.46-49
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• 2009

The desmutagenic activity of the water extract of Cassia tara L on the mutagenicity induced by 4-nitroquinoline 1-oxide (4-NQO) and N-methyl-N-nitro-N'-nitrosoguani-dine (MNNG) was studied using the SOS Chromotest with Escherichia coli PQ37. The inhibition rates of water extract of Cassia tara L. at concentration of $100{\mu}g$/assay were 27.5% and 40% against 4-NQO and MNNG. The water extract of Cassia tara L. was separated into methanol soluble and methanol insoluble parts. The methanol soluble part exhibited higher inhibition effects than the methanol insoluble part against the mutagenic activities of 4-NQO and MNNG. Step-wise fractionation of methanol soluble part was done to obtain methanol, ethyl acetate and water fractions. Among these fractions, water fraction had the strongest inhibitory effects of 23.0 and 19.0% against mutagenicities of MNNG and 4NQO, respectively. The results clearly indicated that the water fraction showed much stronger antimutagenicity against MNNG than 4NQO. The inhibition rates of aqueous fraction of methanol-soluble from water extracted Cassia tara L. at concentrations of 1.0, 10, 100 and $250{\mu}g$/assay were 8.0%, 12.0%, 25.5% and 43.0%, respectively. The water fraction showed the inhibitory effects with dose response against the mutagenic activities induced by MNNG.

• Journal of Plant Biology
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• v.36 no.1
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• pp.105-112
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• 1993

Selection of glyphosate-resistant clones from MNNG-treated mesophyll protoplasts of haploid tobacco and their differentiation were studied. The protoplasts were treated with 0.1 to 100 $\mu\textrm{g}$/mL N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) for 30 min when they expanded to oval shapes. After the treatment, the protoplasts in 4-16 cell stages were transferred to the selective medium containing 1 mM glyphosate for the selection of the glyphosate-resistant colonies. The efficiency of the cell division of the protoplasts in the selective medium decreased as the MNNG concentrations in creased. Optimal MNNG concentration for induction of the glyphosate-resistant clones was 10$\mu\textrm{g}$/mL and mutation frequency was 2.66$\times$10-6. The stability of the glypohsate-resistance of the clones was examined by prolonged subculture in the medium with 1 mM glyphosate, and the resistant clones were survived more than 10 months. Among them one clone has been proliferating and greening and the others were proliferating without greening or greening with slower proliferating.