• Journal of Nutrition and Health
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• v.29 no.2
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• pp.232-241
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• 1996

This study was designed to compare the effect of different dietary fats on plasma lipids, the degree of lipid peroxidation and the activity of antioxidant enzymes in RBC and liver rats treated with or wighout 1, 2-dimethylhydrazing (DMH). Male Sprague Dawley rats, at 7 weeks-old, were divided into control and DMH-treated grous, and each group was again subdivided into four were perilla oil (PO), blend fat (BF) containing ten different kinds of dietary oil, beef tallow (BT), corn oil (CO). At the same time, each rat was injected intramusculary with saline(for control) or DMH twice a week for 6 weeks to give total dose of 180 mg/kg body weight. Compared with BT feeding, BF reduced plasma total choesterol level and PO and Co reduced plasma TG levels (p<0.05). DMH injection decreased plasma cholesterol in all dietary groups. However, PO decreased tocopherol levels and increased TBARS levels in RBC compared to BT. The degree of hemolysis in PO group was higher than that of BT group (p<0.05 only in control group. Fatty acid composition of hepatic microsome was reflected by dietary fatty acid profile. The peroxidizability index and TBARS level in hepatic micorsome were significantly increased but tocopherol level was lowered in PO group compared to BT group. Activites of superoxide dismutase and glutathione peroxidase in RBC and hepatic cytosol were not influenced y dietary fats and DMH treatment(p<0.05). Overall, perilla oil rich in $\omega$3 $\alpha$-linolenic acid could be a very important dietary source in reducing plasma lipids and blend fat was also good dietary oil mixture in reducing plasma cholesterol. However, the degree of lipid peroxidation was greater in tissue by perilla oil feeding and it is very difficult to use only perilla oil as oil source for meal preparation, so that it could be suggested to use more perilla oil and fish to give an equal effect of blend fat in order to reduce the risk factors against cardiovascular disease.

• Food Science and Biotechnology
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• v.15 no.6
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• pp.942-947
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• 2006

The effect of oat bran extracts on the formation of aberrant crypt foci (ACF) in the colon induced by 1,2-dimethylhydrazine (DMH) was studied in F344 male rats. Extracts were prepared using various combinations of temperature (40, 45, 50, 55, or 60$^{\circ}C:\;X_1$), ethanol concentration (0,5, 10, 15, or 20%: $X_2$), and pH (5, 6, 7, 8, or 9: $X_3$). Among the various extracts tested, one ethanol extract (EE; $45^{\circ}C$, 15% ethanol at pH 6) and one water extract (WE; $50^{\circ}C$ at pH 5) were selected based on their in vitro antitumor activity. The animals were fed with basal diet alone or basal diet supplemented with 0.25 or 0.5% of EE or WE for 6 weeks. During the initial 2 weeks of the 6-week test period, the rats were subcutaneously injected with DMH (30 mg/kg) 4 times for the induction of ACF. DMH induced an average of 322.7 and 142.9 aberrant crypts (AC) and ACF, respectively. A low dose (0.25%) of EE (containing 38.3% ${\beta}$-glucan) and WE (containing 22.8% ${\beta}$-glucan) greatly reduced the numbers of DMH-induced AC and ACF. Significantly, ACF consisting of more than 3 AC were reduced by half in which the effect of EE, containing a higher concentration of ${\beta}$-glucan, was superior to that of WE. These results demonstrate that oat bran extracts may confer protection against colon carcinogenesis.

• Journal of Nutrition and Health
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• v.29 no.1
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• pp.112-121
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• 1996

The study was designed to observe the effect of blend fat calculated from the foods consumed in Korean with those of perilla oil, beef tallow and corn oil on colonic mucosal phospholipid fatty acid composition and the levels of TXB2 and diacylglycerol (DAG) which were known as biomarkers for cancer. Male Sprague Dawley rats, at 7 weeks of age, were divided into control and 1, 2-dimethylhydrazine (DMH)-treated group, and each group was subdivided into four groups. The experimental diets contained one of four dietary fats, blend fat (BF), perilla oil(PO), beef tallow (BT) or corn oil (CO), at 15% (w/w) level. At the same time, each rat was injected with saline for control group or DMH twice a week for 6 weeks to give total dose of 180mg/kg body weight. DMH injection, regardless of the type of dietary fats, significantly increased the levels of PGE2 and TXB2 in colonic mucosal layer compared to control (p<0.01). However, the level of eicosanoids was influenced by the types of dietary fats in both control and DMH group. In control groups, colonic mucosal level of TXB2 was higher in beef tallow group, but lower in perilla oil group compared to that of blend fat (p<0.01). In DMH groups, the level of TXB2 was higher in beef tallow and corn oil groups(p<0.05). The level of PGE2 showed the same trends with TXB2 and beef tallow most significantly increased the level of PGE2. DMH treatment did not influence on tissue fatty acid profile, which was directly reflected by dietary fatty acid composition. Proportions of C18 : 2 in colonic mucosal phospholipid well reflected dietary level of C18 : 2 showing the order CO>BF>PO>BT. The precentage of arachidonic acid(AA) in mucosal phospholipid was the highest by CO adn BT groups and the lowest by PO group. The incorporation of $\alpha$-linolenic acid in colonic mucosal phospholipid in perilla oil group was negatively correlated to the content of AA. Dietary level of C18 : 2 might not be the only controlling factor for the production of eicosanoids in colonic mucosa layer and might function with $\omega$3 fatty acids. The level of DAG was significanlty lower in PO group than that of BT group. Therefore, $\omega$3 $\alpha$-linolenic acid rich perilla oil could be very important dietary sourec in controlling eicosanoid production DAG level in cloln and recommenced to use more often in meal preparation to reduce the risk factor against colon cancer.

• Archives of Pharmacal Research
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• v.24 no.6
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• pp.564-567
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• 2001

The fecal ${\beta}-glucuronidase$ activity of patients with colon cancer and healthy controls were measured to determine the relationship between the fluctuation of intestinal bacterial ${\beta}-glucuronidase$ and colon cancer. The fecal ${\beta}-glucuronidase$ activity of patients with colon cancer was 1.7 times higher than that of the healthy controls. However, when these fecal specimens were sonicated, the enzyme activity of patients with colon cancer was 12.1 times higher than that of the healthy controls. The fecal ${\beta}-glucuronidase$ activity of human Intestinal bacteria was drastically induced by its substrate or the bile secreted after a subcutaneous injection of 1,2-dimethylhydrazine (DMH) and benzo[a]pyrene into rats. DMH-and benzo[a]pyrene-treated biles induced ${\beta}-glucuronidase$ activity in the human intestinal microflora by approximately 1.5- and 2.3-fold, respectively. They also induced ${\beta}-glucuronidase$ in E. coli HGU-3, which is a ${\beta}-glucuronidase$-producing bacterium from the human intestine. D-saccharic acid 1,4-lactone similarly inhibited fecal ${\beta}-glucuronidase$ in several patients with colon cancer in addition to the healthy controls. This suggests that potent ${\beta}-glucuronidase$ activity is a prime factor in the etiology of colon cancer.

• Archives of Plastic Surgery
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• v.32 no.6
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• pp.689-698
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• 2005

Many studies for verifying angiogenesis have been in progress, especially in the field of abnormal vascular proliferation to explain the pathogenesis and to develop a treatment of several diseases. In our previous experiments, endothelial cell proliferations were induced by DMH stimulation in vitro, and the 177 factors(142 up-regulated and 35 down-regulated factors) were identified. Among the up-regulated factors, 9 substances (EFEMP1, CTGF, CYR61, $ITG{\beta}1$, FHL2, SERPINE1, MYC, PTTG1 and MSH6) were selected, which were related to cell proliferation and showed high signal intensities. The RNA was isolated from HUVECs at the time of 0, 6, 12, 24 hours after the DMH treatment, and RNA of control group HUVECs was also isolated. Genetic information of selected molecules was used to make primer for each, and RT-PCR was performed to analyze both groups. In control and treatment groups, each substance presented variety of manifestation degree according to time differences. EFEMP1, CTGF, CYR61, $ITG{\beta}1$, FHL2 and MYC were related to abnormal vascular proliferation steadily and SERPINE1, PTTG1 and MSH6 were related secondarily. CTGF was related to both normal and abnormal proliferation, but it played a more significant role in abnormal proliferation from earlier stage. EFEMP1, CYR61, $ITG{\beta}1$, FHL2 and MYC were similar to CTGF, although the relation appeared lately. Further study should be performed to analyze the expressions and the interactions of growth factors, which could be utilized in the new therapeutic development.

• Journal of Nutrition and Health
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• v.31 no.9
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• pp.1394-1403
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• 1998

The study was designed to observe the effect of dietary calcium and fats on plasma cholesterol level, hepatic microsomal fluidity and HMG-CoA reductase activity as well as the excretion of fecal bile acids and neutral sterols in 1, 2-dimethylhydrazine(DMH)-treated rats. Male Sprague Dawley rats, at 7 weeks of age, were divided into 2 groups, 0.3% and 1.0% Ca levels and each group again subdivided into 2 groups of corn oil and perilla oil. Each rat was intramuscularly infused with DMH for 6 weeks to give total dose of 180mg/kg body weight and also fed experimental diet containing 15%(w/w) different fit and Ca(0.3% or 1.0%) for 20 weeks. High dietary calcium(1.0%) did not significantly influence on plasma cholesterol as well as hepatic microsomal fluidity and HMG CoA reductase activity, but significantly reduced the excretion of total bile acid per gram of faces and increased the excretion of total neutral sterol. However, high dietary Ca reduced the excretion of secondary bile acid(deoxycholic and lithocholic acids) which was known as promoter for colon cancer. Perilla oil rich in n-3 ${\alpha}$-linolenic acid significantly decreased plasma cholesterol by increasing hepatic microsomal fluidity compared with corn oil, but did not influence on HMG CoA reductase activity. Perilla oil did not influence on fecal excretion of total and primary bile acids, but reduced the excretion of secondary bile acids. Therefore, it could be recommended to consume more fish product and food rich in calcium and use more perilla oil in meal preparation to prevent from coronary hear disease and colon cancer especially when high fit diet has been practiced. (Korean Nutrition 31(9) : 1394-1403, 1998)

• The Korean Journal of Food And Nutrition
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• v.9 no.1
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• pp.59-68
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• 1996

The study was designed to observe the effects of different dietary fat consumed in Korea with those of three other fats on colonic epithelial cell phospholipid and phosphatidyl inositol composition, which were known as biomarker for colon cancer. Male Sprague Dawley rats, at 7 weeks of age, were divided into control and 1,2-dimethylhydrazine (DMH) -treated group that was again subdivided into four groups. The experimental diets contained one of four dietary fats at 15%(w/w) level, those were, blend fat(BF), beef tallow(BT), corn oil (CO) or perilla oil (PO) At the same time, each rat was injected nth saline for control group or DMH twice a week for 6 weeks to five total dose of 180 mg/kg body weight. Dietary fatty acid composition influenced the fatty acid compositions of tissues. Proportions of C18:2 colonic mucosal phospholipid well reflected dietary level of C18:2 showing in decending CO>BF>PO> BT. The percentage of C20:4 in phospholipid was the higher in CO and BT groups and the lowest in PO groups. Incorporation of -linolenic acid in colonic mucosal lipid In perilla oil group was negatively correlated to the content of C20:4. Therefore, $\omega$3-linolenic acid rich in perilla oil could be a very important dietary source in controlling arachidonic acid level in colon epithelial cell. Therefore it could be recommend to use more perilla oil in meal preparation to reduce the risk factor against colon cancer.

• Archives of Plastic Surgery
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• v.34 no.1
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• pp.13-17
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• 2007

Purpose: To understand the pathogenesis of the disease that presents abnormally proliferated vascular endothelial cells, a model of DMH(1,2-dimethylhydrazine)-induced abnormal proliferation of HUVECs(Human Umbilical Vein Endothelial Cells) was made. We indirectly determined that Protein Kinase C(PKC) restricts the cellular proliferation and inhibits the manifestation of growth factor by using several inhibiting substances of the transmitter through our previous studies. Thereupon, we attempted to observe direct enzymatic activities of PKC and its correlation with the abnormal proliferation of vascular endothelial cells. Methods: $10^5$ HUVECs cells were applied to 6 individual well plates in three different groups; A control group cultured without treatment, a group concentrated with $0.75{\times}10^{-8}M$ DMH only, and a group treated with DMH & $5{\times}10^{-9}M$ Calphostin C, inhibitor of PKC. In analyzing the formation of intracellular PKC enzyme, protein separation was performed, and separated protein was quantitatively measured. PKC enzyme reaction was analyzed through Protein Kinase C Assay System (Promega, USA), and the results were analyzed according to Beer's law. Results: Enzymatic activity of PKC presented the highest in all reaction time of a group concentrated only with DMH, and the lowest in the control group. The group treated with DMH and the inhibitor revealed statistically lower enzymatic activity than group only with DMH in all reaction time, although higher than the control group. Conclusion: From the enzymatic aspect, most active and immediate reaction of the PKC was observed in the group concentrated with DMH only. The group treated with DMH & PKC inhibitor showed meaningful decrease. Accordingly, PKC holds a significant role in DMH-induced abnormal proliferation of vascular endothelial cells.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.73-80
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• 2016

Colorectal cancer is a very prevalent diagnosed cancer. The current study was performed in order to examine the role of BRAE (Basella rubra aqueous extract) in regulating aberrant crypt foci (ACF) formation, cell proliferation and inhibition of apoptosis in a colon carcinogenesis model in male Wistar rats. Rats were randomly allocated into six groups. Group I served as control, and group II acted as a drug control administered BRAE (250mg/kg b.w.) orally for 30 weeks. Rats in group III-VI were given subcutaneous injections of DMH (25mg/kg b.w. weekly) for 15 weeks to initiate colon carcinogenesis. Those in group IV and VI were administered BRAE along with DMH injections. Rats in group V were administered with BRAE after cessation of DMH injection. After 30 weeks of experimental period colons were obtained from experimental groups and analyzed for ACF incidence, argyrophilic nucleolar organizing region-associated proteins (AgNOR) count, histopathological and immunohistochemical changes. Only in DMH exposed groups were ACF and AgNOR numbers increased. Administration of BRAE appreciably decreased the numbers of ACF and AgNOR in BRAE treated groups. Histopathological findings revealed a high level of dysplastic changes with decreased number of goblet cells found only in only DMH injected rats. Administration of BRAE in treated group rats reversed these changes. Expression markers for cell proliferation (PCNA and Ki67) were elevated in DMH treated rats, but reduced with BRAE treatement. This expression was reversed with apoptosis markers (p53 and Caspase-3). Thus the results results of the present study were found to be significant and confirmed the potential efficacy of BRAE against colon carcinogenesis.

• Journal of Nutrition and Health
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• v.36 no.7
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• pp.661-666
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• 2003

The study was designed to compare the anti-carcinogenic effect of conjugated linoleic acid (CLA) isomers on colon carcinogenesis in 1,2-dimethylhydrazine (DMH)-treated rats by determining the levels of apoptosis, cell proliferation, eicosanoids and 1,2-diacylglycerol (DAG) in colonic mucosa. Sixty male Sprague Dawley rats were randomly divided into 3 groups depending on the types of CLA isomers, i.e. BT group (no CLA contained), CLA-C group (cis-9, trans11 isomer contained), and CLA- T group (trans-10, cis-12 isomer contained). The experimental diet was composed of protein at 20%, carbohydrate at 56.2%, and fat at 14.5% including 0.8% CLA isomers by weight. The experimental diet was fed for 14 weeks with the initiation of intramuscular injection of DMH, which was injected twice a week for 6 weeks to give total dose of l80mg per kg body weight. Two CLA isomers (c9t11 and t10c12) significantly increased the relative percentage of apoptosis but reduced cell proliferation in mucosal cell and also the levels of PGE$_2$, TXB$_2$, and DAG in colonic mucosa. However, there was no significant differences in anti-carcinogenic effect between c9t11 isomer and t10c12 isomer. Overall, colon carcinogenesis could be significantly inhibited by CLA isomers by increasing apoptosis and reducing cell proliferation, the levels of eicosanoids and DAG in colonic mucosa.