• 대한수의학회지
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• 제37권1호
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• pp.167-176
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• 1997

The present investigation was focussed mainly on the development of the tumors and proliferating cells on the intestinal tracts of 1, 2-dimethyl-hydrazine(DMH)-treated young or adult rats. 26 rats(Wistar, 14 young rats weighting approximately 130~180gm and 12 adult rats weighting approximately 500~550gm) were given subcutaneously once weekly with 20mg of DMH/kg body weight(BW)/week for 8~22 weeks. Individual body weight were recorded weekly at the same day and time. The rats were killed at 8, 13, 15. 17, 19, 21 and 22 weeks. The intestinal tracts were opened longitudinally and carefully examined for tumors. The localization, number, and size of tumors were noted. Tumor-bearing areas were dissected out and fixed on neutral buffered 10% formalin and normal-looking mucosa from 8~22 weeks rats were also taken for fixation. Paraffin sections were stained by H-E for histopathological examination or with immunohistochemical stain for bromodeoxyuridine(Brdur) positive cells. 1. The growth proportion of body weight appeared to be decreased in the DMH-treated young rats than in control young rats and body weight of DMH-treated adult rats appeared to be 13.4% or less lower than weighted on 0 week. 2. Macroscopically, the developed tumors in the intestinal tracts were not observed as early as the 13 weeks after DMH treatment. The number of developed tumors per rat was found to be 14.3, 18.8, 22.3 in 15, 17 and 22 weeks. The numbers of tumors in intestinal regions per rat were 2.1, 4.3, 5.4, 2.5 in duodenum, jejunum, ilium and colon on 15 weeks, 2.3, 6.4, 7.8, 2.3, on 17 weeks, and 2.7, 9.3, 9.0, 1.3 on 22 weeks, respectively and the ileum and jejunum were higher in appearance rate of tumors and tumor types are dome shapes and diameter of largest tumor were 6.3mm. 3. Histopathologically, intestinal mucosa were thickened by the irregular distorted and distended crypts following hyperplasia. The tumors developed on the mucosa and submucosa and were recognized to be adenocarcinoma. 4. Immunohistochemically, the labeling index(LI) was calculated as the ratio of the number of Brdur-labeled cells to the total number of column cells of the crypts with longitudinal axis. LI of Brdur positive cells per crypt were 5.6%, 8.0% on small intestine of control and 22 week group, respectively and 3.7%, 12.7% on large intestine of control and 22 week group, respectively and were appeared to be increase in 22 week group than in control group and to be more number of proliferating cells in 22 week group than in control group. 5. LI of Brdur positive cells in 1, 2, 3, 4, 5 segments of crypt column were 11.7%, 10.7%, 3.8%, 0.6%, 0% in small intestine of control group and 23.5%, 11.8%, 2.3%, 2.4%, 0.8% in small intestine of 22 week group, and 5.4%, 7.4%, 3.8%, 1.0%, 0.4% in large intestine of control group and 29.5%, 20.3%, 5.9%, 6.3%, 1.3% in large intestine of 22 week group respectively. So results indicate that the number of proliferating cells by DMH treatment increase and were concentrated on the 1, 2 segments of crypt columns.

• Archives of Pharmacal Research
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• 제18권2호
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• pp.79-83
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• 1995

There is epidemilogical evidence that the population with high fecal ${\beta}-glucuronidase$activity has greater risk of colon cancer than the population with low facal ${\beta}-glucuronidase$. This relationship was investigated by using the mouse-dimethylhydrazine colon carcinogenesis model and the fraction of Glucidum which is a .${\beta}-glucuronidase$inhibitor. Mice with low facal ${\beta}-glucuronidase$activity induced by consumption of the ether fraction of G lucidum had significantly fewer aberrant crypts(AC) after injections of 1, 2-dimethylhydeazine (DMH) than mice treated with DMH alone. The result supports the hypothesis that the inhibitor such as the ether fraction of G lucidum can protect an animal against the induction of colon cancer.

• Preventive Nutrition and Food Science
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• 제13권3호
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• pp.157-165
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• 2008

Cancer-preventive effects of ethanol extract of elm tree root (EEE) were investigated. In the in vitro cytotoxicity assay, colon cancer cells were incubated with a chloroform fraction of EEE (CF-EEE). CF-EEE significantly inhibited the proliferation of cells and induced apoptotic cell death in a dose-dependent manner. For the assessment of chemopreventive efficacy in vivo, male F344 rats were fed with EEE (0.5 or 1%) in diet for 8 weeks, and were subcutaneously injected with 1,2-dimethylhydrazine (DMH) to induce colonic aberrant crypt foci (ACF). EEE (0.5 and 1%) significantly decreased both the numbers of AC (1191.1/colon) and ACF (529.3/colon) induced by DMH. In addition, in the Western blot analysis on the colonic mucosa, administration of EEE triggered expression of caspase-3, a key factor of an apoptotic cascade. These results suggest that extract of elm tree root may have potential chemopreventive principles that lead to apoptosis of cancer cells, and thereby suppress colorectal carcinogenesis during the initiation stage.

• Archives of Plastic Surgery
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• 제34권6호
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• pp.679-684
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• 2007

Purpose: DMH(1,2-dimethylhydrazine) has been known to induce vascular neoplasm such as malignant endothelioma in animal experiment, through induction of abnormal proliferation of HUVECs. In our previous studies, 11 types of PKC isoenzymes were determined by RT-PCR and the expression of $PKC{\alpha}$, and ${\mu}$ was more prominent than other PKC isoenzymes in the DMH-treated group. However, this result was not based on objective assessment. In this study, we further evaluated the role of $PKC{\alpha}$ on the DMH-induced abnormal proliferation of HUVECs by two different methods to identify its presence with high relevance in objective view. $PKC{\mu}$ will be investigated in further study. Methods: The study was conducted with the cultured HUVECs group(control) and the $0.75{\times}10^{-9}M$ DMH-treated group. After processing protein extraction in 0 and 24 hour, extracted protein was treated of quantitative test through BCA protein assay. In the western blot analysis, electrophoresis was performed in the order of gel preparation, sample preparation, and gel running. Electrotransfer to nitrocellulose membrane and reaction with antibody were done. Detection of $PKC{\alpha}$ was achieved through "Gel Image Analysis System". In the fluorescence immunocytochemical analysis, the grading of radiance of the intracellular $PKC{\alpha}$ particles was detected with confocal microscope after treating with primary and fluorescent secondary antibody in 0 and 24 hours. Results: The Western blot analysis showed increased $PKC{\alpha}$ expression from the specimen obtained in 24 hour of the DMH treatment group when compared to those in control group. Under confocal fluorescence microscope, the emitting radiance in the DMH treated group was brighter at 24 hours as well. Conclusion: We believe that $PKC{\alpha}$ plays a role in DMH-induced abnormal proliferation of the vascular endothelium, which may provide insights in understanding the vascular neoplasm.

• Journal of Nutrition and Health
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• 제35권10호
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• pp.1038-1044
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• 2002

The study was designed to observe the effect of conjugated linoleic acid (CLA) on tumor incidence, eicosanoid formation and antioxidant enzyme activities in colonic mucosa and the fecal excretion of deoxycholic acid and lithocholic acid in 1,2-dimethylhydrazine (DMH)-treated rats. One hundred twenty male Sprague Dawley rats were divided into 2 groups, BT (beef tallow diet) group and FO (fish oil diet) group, and each group was again subdivided into 2 groups depending on CLA supplementation, i.e.4 groups of BT, BTC, FO, FOC. All rats were fed experimental diet for 30 weeks, which contained 12% (wt/wt) total dietary fat including 1% (wt/wt) CLA, and were intramuscularly injected with DMH for 6 weeks to give total dose of 180 mg/kg body. CLA-supplemented to BT and FO diet reduced tumor incidence, eicosanoid (PGE$_2$ and TXA$_2$) level in colonic mucosa. N-3 fatty acids (mainly DHA) of fish oil diet (FO, FOC group) also reduced tumor incidence and significantly reduced eicosanoid (PGE$_2$ and TXA$_2$) level in colonic mucosa. CLA supplementation and n-3 fatty acid significantly increased colonic mucosal level of superoxide dismutase and glutathione peroxidase activities but reduced secondary bile acids (deoxycholic acid and lithocholic acid) excretion in the feces. In conclusion, CLA supplementation and n-3 fatty acid could reduce tumor incidence by reducing eicosanoids and increasing antioxidant enzyme activities in colon and decreasing the excretion of deoxycholic acid and lithocholic acid in the feces. The data might suggest that CLA supplementation and n-3 DHA rich fish oil may modulate colon carcinogenesis.termediate level of endurance exercise training for 6 weeks did not influence concentrations of most of free amino acid in soleus muscle of rats collected at an overnight fasted and rested state. In contrast, isolucine and leucine concentrations in extensor digitorum longus muscle of exercise-trained rats were significantly lower than those for control animals. These results indicate that aerobic energy metabolism had not been efficiently conducted, and thereby the utilization of BCAA for energy substrate was enhanced in fast twitch oxidative glycolytic fibers of extensor digitorum longus muscle of rats followed exercise-training protocol for 6 weeks.

• 한국식품영양과학회지
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• 제38권7호
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• pp.839-845
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• 2009

오만둥이는 우리나라의 전통적인 수산식품으로써 찜 또는 찌개류로 조리하여 널리 이용하여 왔다. 본 연구에서는 오만둥이의 기능성 소재로서의 기능적 특성을 파악하기 위하여 오만둥이 추출물의 항산화 활성 및 항유전독성 활성을 in vitro 방법으로 측정하였다. 또한 대장암에 대한 예방효과를 알아보기 위하여 DMH로 대장암을 유발한 SD 쥐를 이용하여 오만둥이를 경구투여한 후 DNA 손상 및 ACF 형성에 미치는 영향을 알아보았다. 그 결과 총항산화능은 모든 추출물에서 대조구에 비해 유의적으로 높은 활성을 나타내었다. 동결건조 한 추출물에서는 메탄올, 에탄올(0.225, 0.219 mM) > 물(0.179 mM) > 아세톤(0.150 mM) 순으로 나타났으며, 신선한 오만둥이에서는 메탄올 추출물(0.215 mM)이 가장 높은 항산화력이 있는 것으로 나타났다. Comet assay에서는 모든 추출물이 $H_2O_2$에 의한 산화적 스트레스에 대항한 DNA 손상억제력을 향상시키는 것으로 나타났으며 특히 동결건조 한 오만둥이에서 메탄올 추출물의 억제력이 가장 높은 것으로 나타났다. 백혈구의 DNA 손상정도는 대조군에 비해 DMH 투여군에서 유의적으로 손상정도가 증가한 반면, DMH+S. placata군에서는 DMH를 주입한 군에 비하여 손상정도가 유의적으로 감소하였다. 또한 ACF의 생성수치가 DMH군에 비하여 DMH+S. placata군에서 유의적으로 감소하는 결과를 나타내었다. 이상의 결과로 미루어 볼 때 오만둥이는 in vitro 뿐만 아니라 대장암을 유발한 쥐에서도 항산화 및 항암효과에 긍정적인 영향을 미치는 것으로 나타나 오만둥이가 대장암을 예방하기 위한 기능성식품 소재로서 가능성을 보여 주었다.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Effects of Edible Phytochemicals and Their Synthetic Derivatives on Carcinogenesis and Mutagenesis
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• pp.5-6
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• 2001

The carcinogens 2-arnioo-3-methylimidazo［4,5-f］quinoline (IQ) and 1,2-dimethylhydrazine (DMH) induce colon tumors in the Fisher 344 rat that contain mutations in Ctnnb1, the gene for b-catenin, but the pattern of mutation differs from that found in human colon cancers. in both species, mutations affect the glycogen synthase kinase 3$\beta$ (GSK-3$\beta$) consensus region of $\beta$-catenin, but whereas they directly substitute critical Ser/Thr phosphorylation sites in human colon cancers, the majority of mutations cluster around Ser$^{33}$ in the rat tumors.(omitted)

• 한국수의병리학회지
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• 제5권1호
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• pp.23-28
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• 2001

This study was conducted to assess the chemopreventive effects of sodium selenite in the rat medium-term multi-organ bioassay using a DMBDD model (DEN+MNU+BBN+DMH+DHPN). Seventy five,6-week-old, male SD rats were divided into 3 groups. The animals in group 1 received DEN(diethylnitrosamine,100 mg/kg bw, single i.p., in saline), MNU (N-methyl-nitrosourea,20 mg/kg bw, i.p.,4 times for 2 weeks), BBN (N-butyl-N-(4-hydroxybutyl) nitrosamine, 0.2% in drinking water for 2 weeks), DMH (1,2-dimethylhydrazine, 40 mg/kg bw, s.c., in saline.4 times (or 2 weeds), and DHPN (N-bis(2-hydroxy-pro-pal)nitrosamine,0.1% in drinking water for 2 weeks), then were placed on sodium selenite (4 ppm in drinking water) for 22 weeks from weeks 4 to 26. The animals in group 2 were given DMBDD alone. The animals in group 3 were given sodium selenite alone. Animals were sacrificed at week 12 for ACF quantitative analysis and at week 26 for tumor induction. The body weights in the group 1 were significantly decreased compared with those of group 2. The tumor multiplicities of large intestine in the group 1 were significantly decreased compared with those of group 2 (P<0.05). These results indicate that sodium selenite may have a potential as chemopreventive agents of colon carcinogenesis.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Dietary and Medicinal Antimutgens and Anticarcinogens
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• pp.48-49
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• 2001

The carcinogens 2-amino-3-methylimidazo［4, 5-f］quinoline (IQ) and 1, 2-dimethylhydrazine (DMH) induce colon tumors in the Fisher 344 rat that contain mutations in Ctnnbl, the gene for b-catenin, but the pattern of mutation differs from that found in human colon cancers. In both species, mutations affect the glycogen synthase kinase 3$\beta$ (GSK-3$\beta$) consensus region of $\beta$-catenin, but whereas they directly substitute critical Ser/Thr phosphorylation sites in human colon cancers, the majority of mutations cluster around Ser$_{33}$ in the rat tumors.(omitted)d)

• Nutritional Sciences
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• 제4권2호
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• pp.73-78
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• 2001

This study investigated the effect of different dietary fats and fibers on colon tumor incidence and cell proliferation, the levels of eicosanoids and polyamines in colonic mucosa of DMH-treated rats. The experiment was conducted on male Sprague Dawley rats using a 2 $\times$3 factorial design with two fats (corn oil and DHA-rich fish oil) and two fibers (cellulose and pectin) and a fiber-free control. The rats were find an experimental diet containing 15% (w/w) dietary fat and 6% (w/w) fiber for 25 weeks. Tumor incidence was Bower in rats fed fish oil as opposed to corn oil. The levels of arachidonic acid (AA) and eicosanoids ($PGE_2, and TXB_2$) in normal colonic mucosa were significantly lower in rats fed fish oil and there was a concomitant increase of docosahexaenoic acid (DHA). The levels of eicosanoids and AA in tumor tissues were significantly higher than those of normal colonic mucosa. The level of polyamines in normal colonic mucosa was not affected by dietary fats but was significantly lower than that in rumor tissues. Dietary fiber did not have a significant effect on rumor incidence and the levels of AA, eicosanoids and polyamines. Overall, fish oil rich in DHA reduced cell prolifiration and thus inhibited colon carcinogenesis through its effect on the distribution of AA and production of eicosanoids in normal colonic mucosa. However, its effect on colon carcinogenesis revealed a lack of consistency depending on the type of dietary fiber in diet.