• YAKHAK HOEJI
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• v.39 no.1
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• pp.94-101
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• 1995

In order to evaluate the suppressive effects of galangin on the DNA damage induced by N-methyl-N-nitrosourea(MNU), in vitro sister chromatid exchange(SCE) test using Chinese Hamster ovary(CHO) cells was performed. Also the determinations of [$^{3}$H] MNU-induced total DNA binding and methylated DNA were performed to find out the mechanism of action by galangin. MNU-induced SCEs were significantly decreased by simultaneous and pretreatment of galangin when S-9 mix was added only. In post-treatment, however, the MNU-induced SCEs were not decreased when S-9 mix was added or not. [$^{3}$H] MNU-induced total DNA binding was significantly inhibited by the treatment of galangin in calf thymus DNA and CHO cells. HPLC analysis of DNA hydrolysates shows that galangin caused a dose-dependant decrease in calf thymus DNA, but not significant decrease in CHO cells. These results suggest that the inhibition of galangin on the MNU-induced SCEs is due to the decrease of DNA binding and methylation with MNU. Therefore, galangin may be useful as a chemopreventive agent of alkylating agents.

• Journal of the Korean Chemical Society
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• v.39 no.11
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• pp.842-847
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• 1995

The electrochemical reduction reactions of N '-aryl-N-alkyl-N-nitrosourea derivatives with a glassy carbon electrode were diffusion controlled and irreversible. The exchange kinetic constant ko values for reduction reaction of the N '-aryl-N-alkyl-N-nitrosoureas were at the range of $1.48{\times}10^{-6}{\sim}5.32{\times}10^{-7}\;cm/sec.$ The $k_0$ values for phenyl substituted on the aryl position were about 1.3∼2.8 times higher than that of other substituents. The same substituent for aryl groups on the both of N '-aryl-N-alkyl-N-nitrosourea and N '-aryl-N-(2-chloroethyl)-N-nitrosourea exhibited same value. The $E_p$ value was shifted to the negative direction as pH increased. The number of protons participated to the reduction was 4∼5, respectively. The substituent effect of aryl group on the reduction potential was not observed in this case.

• The Korean Journal of Zoology
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• v.24 no.3
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• pp.163-171
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• 1981

Chromosome aberrations induced by ENU and MNU were investigated in CHO cells at various doses and times after treatment. The results obtained were as follows: The frequency of chromosome aberrations induced by ENU and MNU drastically depends on the length of the post-treatment period and the concentration of these chemicals. In ENU-treated groups, the major type of aberration was chromatid deletions in earlier samples but the frequency of chromatid exchanges increased with time, revealing, predominant type at 24 hours after treatment with $10^-3$ M. In MNU-treated groups, chromatid deletions were also major type but frequency of chromatid exchanges were predominant from 12 hours after treatment with $10^-4$ and $10^-5$ M.

• Toxicological Research
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• v.16 no.4
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• pp.275-284
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• 2000

The organ culture model of the whole mammary gland has many advantages for the study of branching morphogenesis and biological characteristics, including tumorigenesis. Prior to whole gland organ culture, rats were treated with 7,12-dimethylbenz[a]anthracene (DMBA) or N-methyl-N-nitrosourea (MNU) for one week. The tramdorming effect and the morphological changes were assessed by the whole mount preparations and histopathological examination in terminal end buds (TEB), terminal ducts (TD), alveolar buds (AB), alveolar lobules (AL) and hyperplastic alveolar nodules (HAN) of the mammary gland. Grossfindings of the mammary glands at dissection were higher branching morphogenesis and larger volume in carcinogen-treated groups than in carcinogen-non-treated groups. Results of the whole mount method were coincided with those of the histopathological observations. Circular TEB, normally maintained AB, AL, and high cellular density were more frequently observed in carcinogen-treated groups than in carcinogen-nan-treated groups. Histopathologically, as a preneoplastic marker, HAN was maintained only in mammary organ culture of the carcinogen-treated groups. These findings suggest that in vivo trans-formation effects by carcinogens persisted during the mammary organ culture. These results were more characteristic in DMBA than in MNU-treated group. Ducts and terminal ducts appeared to have lost morphology during their growths in case of without diethylstilbestrol (DES). The fact that in vitro organ culture without DES was resulted in abnormal ductular morphogenesis confirms that DES is a physiological regulator of ductular epithelial cell growth.

• Environmental Mutagens and Carcinogens
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• v.18 no.2
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• pp.77-82
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• 1998

In order to compare the suppressive effect of galangin on the genotoxicity by N-methyl-N-nitrosourea (MNU) or benzo[a]pyrene B(a)P, in vivo micronycleus test using mouse peripheral blood and in vitro sister chromatid exchange(SCE) test using mouse spleen lymphocytes were performed. MNU or B(a)P-induced micronucleated reticulocytes in vivo was decreased by the simultaneous treatment of galangin. MNU or B(a)P-induced SCEs in vitro was also decreased by the simultaneous treatment of galangin. On the other hand, the determinations of [$^3$H]MNU-induced total DNA binding and methylated DNA were performed to find out the mechanism of action. [$^3$H]MNU-induced total DNA binding was inhibited by the treatment of galangin in calf thymus DNA. HPLC analysis of DNA hydrolysates showed that galangin caused a decrease of 7-methyl guanine and $O^{6}$-methyl guanine in calf thymus DNA. To elucidate the action mechanism of galangin against B(a)P, alteration of B(a)P metabolism was studied. Galangin inhibited B(a)P metabolism in the presence of S-9 mix and decreased B(a)P-DNA binding in calf thymus DNA with S-9 mix.

• Proceedings of the Korean Society of Crop Science Conference
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• 1990.10a
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• pp.8-9
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• 1990

• Journal of Food Hygiene and Safety
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• v.13 no.3
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• pp.243-251
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• 1998

Panax ginseng C.A. Meyer has been extensively used in the traditional oriental medicine as a restorative, tonic and prophylatic agent. Petroleum ether extract of panax ginseng C.A. Meyer (GPE) and its several fractions (PI-P5) were tested for the evaluation of antigenotoxicity against N-methyl-N-nitrosourea (MNU) and benzo(a)pyrene [B(a)P]-induced micronucleated reticulocytes in mouse peripheral blood. GPE and P2 showed more significant anticlastogenicity than other fractions did. To elucidate the anticlastogenic action mechanism of GPE and P2 against B(a)P, the alteration of B(a)P metabolism was studied. GPE and P2 inhibited B(a)P metabolism in the presence of 8-9 mix and decreased B(a)P-DNA binding in calf thymus DNA with 8-9 mix. They also decreased [$^3H$] MNU induced DNA binding and methylation to 7-methyl guanine and $O^{6}-methyl$ guanine adducts in calf thymus DNA by RPLC analysis. These results suggest that the anticlastogenicity of GPE and P2 on the B(a)P or MNU-induced clastogenicity is due to decrease of DNA binding with B(a)P or MNU, the inhibition of metabolism with B(a)P and the inhibition of methylation in DNA. Therefore, GPE and P2 may be useful chemopreventive agents of alkylating agent like MNU and secondary carcinogen like B(a)P.

• Proceedings of the Korean Society of Life Science Conference
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• 2008.10a
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• pp.71.1-71.1
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• 2008

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6721-6726
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• 2014

Background: The aim of this preliminary study was to address variations of responses observed with different starting tumor sizes of 10 and 15 mm, and the effects of different doses of tamoxifen (TAM) on experimental rat mammary tumors. Materials and Methods: Thirty-five inbred female Sprague Dawley rats aged 43 days were administered with three weekly doses of N-methyl-N-nitrosourea (NMU) intraperitoneally (ip) at 50 mg/kg body weight. Animals were randomized (beginning from 10 mm tumor size) into four TAM-treated (50, 100, 200 and $500{\mu}g/day$) groups of six animals each, and another group (n=6) treated with TAM $100{\mu}g/day$ at starting tumour size of 15 mm. The animals were treated by oral gavage daily for 8 weeks before sacrifice. Results: Serum urea and creatinine, and overall physical tumor burden were significantly modulated in animals treated with variable doses of TAM compared to the untreated controls (n=5). Final body weight and tumor number were significantly different in the 10 mm-treated animals compared to those treated at 15 mm. There were no significant differences in histopathological features among all the groups. Conclusions: Our findings suggest the importance of standardizing tumour size and drug doses before initiation of treatment, particularly in the direct comparison of basic end-tumour physical parameters.

• Natural Product Sciences
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• v.4 no.2
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• pp.105-114
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• 1998

The antimutagenic activity of a methanol extract of Ecklonia stolonifera (Laminariaceae) against aflatoxin $B_1\;(AFB_1)$ was demonstrated with the Salmonella typhimurium assay. The numbers of revertants per plate decreased significantly when this extract was added to the assay system using S. Salmonella typhimurium TA100. The methanol extract also exhibited significant inhibitory effects on the micronuclei formation in mouse peripheral blood reticulocytes and the DNA damage in mouse spleen lymphocytes induced by N-methyl-N-nitrosourea (MMU) and benzo(a)pyrene (B(a)P). The MeOH extract was then sequentially partitioned with $CH_2Cl_2,\;CH_2Cl_2$ insoluble intermediate, EtOAc, n-BuOH, and $H_2O$. All fractions possessed antimutagenic activity but the $H_2O$ fraction was inactive. Among active fractions, the EtOAc and $CH_2Cl_2$ insoluble intermediate fractions showed the highest activity. Column chromatography using $SiO_2$ and Sephadex LH-20 yielded phloroglucinol from the EtOAc fraction. Phloroglucinol also demonstrated significant antimutagenic activity, and inhibitory effects on the micronuclei formation in mouse peripheral blood reticulocytes and DNA damage in mouse spleen lymphocytes induced by MMU and B(a)P.