Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aberrant crypt foci, consisting of morphologically irregular crypts, are thought to be precancerous lesions for colorectal cancers. For analysis of individual crypts, F344 rats were administered weekly subcutaneous injections of 1,2-dimethylhydrazine ten times and sacrificed at experimental weeks 10 and 20 with 5-bromo-2'-deoxyuridine (BrdU) incorporation 1 h before the sacrifice. Isolated colonic crypts were classified into hexosaminidase-altered aberrant crypts (HAACs) and hexosaminidase-preserved normal-appearing crypts (HPNCs) and stereopaired images (tilt angle, 6 degrees ) were taken with a scanning electron microscope for three-dimensional analyses. While HPNCs showed symmetrical fission at the base, HAACs exhibited abnormal budding in the middle of the crypt body. At week 10, average BrdU labeled cells per crypt for DMH-treated HPNCs and HAACs were 4.9 +/- 1.0 and 18.7 +/- 2.2 (P < 0.0001), respectively, while the value for non-treated control crypts was 14.7 +/- 0.8/crypt. BrdU-positive cell numbers per unit crypt length (100 microm) in HPNCs and HAACs were 1.75 +/- 0.37 and 5.99 +/- 0.70 (P < 0.0001), respectively, while that for the control was 6.65 +/- 0.35 (P < 0.02 vs. HAAC). At the 20-week time point, the numbers per crypt were 4.0 +/- 0.8, 10.1 +/- 1.6, and 27.4 +/- 2.4, respectively, the control value being significantly higher than the others (P < 0.0001). The figures per unit length were 1.72 +/- 0.35, 2.92 +/- 0.42, and 13.39 +/- 1.11 (P < 0.0001 vs. HAAC and HPNC), respectively. BrdU incorporating cells were distributed in the bottom third of the crypt columns in HAACs, but only 18% in the HPNCs, providing evidence of hyperplasia. HAACs could be good surrogate indicators of carcinogen exposure, at least some of which may be related to colon carcinogenesis.
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PMID:Three-dimensional analysis of isolated hexosaminidase-altered aberrant crypts from colons of 1,2-dimethylhydrazine-treated rats. 1641 54

We investigated the chemopreventive potential of luteolin on hepatic and circulatory lipid peroxidation and antioxidant status during 1,2-dimethylhydrazine induced colon carcinogenesis in rats. Rats were given a weekly subcutaneous injection of DMH at a dose of 20 mg/kg body weight for 15 weeks. Luteolin (0.2 mg/kg body weight/everyday p.o.) was given at the initiation and also at the postinitiation stages of carcinogenesis to DMH treated rats. The animals were sacrificed at the end of 30 weeks. Enhanced lipid peroxidation in the liver and circulation of tumor bearing rats was accompanied by a significant decrease in the levels of plasma and hepatic reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), vitamin C, vitamin E and beta-carotene in DMH treated rats as compared to the control rats. Intragastric administration of luteolin (0.2mg/kg body weight) to DMH-treated rats significantly reduced the incidence and size of tumor in the colon, reduced lipid peroxidation levels and enhanced the plasma and hepatic activities of GSH, GPx, GST, GR, SOD, CAT, vitamin C, vitamin E and beta-carotene. Thus the chemopreventive efficacy of luteolin against colon carcinogenesis is evidenced by our preliminary studies which showed decreased incidence of tumors and the antiperoxidative and antioxidant effect of luteolin. Further study on the exact mechanism of action of luteolin in preventing colon carcinogenesis is yet to be elucidated.
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PMID:Chemopreventive potential of luteolin during colon carcinogenesis induced by 1,2-dimethylhydrazine. 1668 36

Selective inhibitors of cyclooxygenase-2 (COX-2) enzyme activity have shown chemopreventive activity in carcinogen-induced and transgenic rodent tumor models and clinically for colon cancer. However, the mechanism(s) by which COX-2 inhibitors reduce carcinogenesis remains controversial. We report herein that administration of the selective COX-2 inhibitor, celecoxib, significantly reduces the number of Gr1(+)CD11b(+) immature myeloid suppressor cells (IMSCs) during chemoprevention of 1,2-dimethylhydrazine diHCl-(1,2-DMH-) induction of large intestinal tumors in Swiss mice. Celecoxib administration also increased splenic lymphatic number and tumor infiltration by lymphocytes. The 1,2-DMH induction of large intestinal tumors was associated with a four-fold increase in IMSCs, and a decrease in splenic T cell number and function. Concordant with the changes in the IMSC frequency, messenger ribonucleic acid (mRNA) levels of inducible nitric oxide synthase (NOS-2) and arginase (Arg) were increased in the spleen of the tumor-bearing mice and normalized by celecoxib administration. In addition to delaying tumor induction, reducing tumor number, and increasing lymphocyte infiltration of tumors, celecoxib therapy reversed CD4(+) T cell loss, decreased IMSC numbers and increased mRNA levels of NOS-2 and Arg in the spleen. In summary, our results suggest that celecoxib chemoprevention of autochthonous intestinal tumors can regulate IMSCs and CD4(+) T cell numbers.
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PMID:Chemoprevention by cyclooxygenase-2 inhibition reduces immature myeloid suppressor cell expansion. 1717 80

Bacillus polyfermenticus has been used in an effective treatment for long-term intestinal disorders, as live strains in the form of active endospores have been shown to reach the target intestine successfully. In this study, we have assessed the effects of B. polyfermenticus on the antioxidant system and the process of colon carcinogenesis in male F344 rats. The rats were divided into three groups after a 1-week adaptation period, and were then fed on either a high-fat and low-fiber diet (control and DMH groups), or a high-fat and low-fiber diet supplemented with B. polyfermenticus (3.1x10(8) cfu/d) (DMH+B. polyfermenticus group). One week after beginning the diets, the rats were subjected to 6 weeks of treatment with 1,2-dimethylhydrazine (DMH, 30 mg/kg/week, s.c.). The dietary treatments continued over the entirety of the experimental period. Nine weeks after the initial DMH injection, the rats supplemented with B. polyfermenticus evidenced significantly lower numbers of aberrant crypt foci than were observed in the DMH group. Injections with DMH resulted in significantly higher leukocytic DNA damage and plasma lipid peroxidation levels, as well as a lower plasma total antioxidant potential, and these factors recovered as the result of supplementation with B. polyfermenticus. These data indicate that B. polyfermenticus exerts a protective effect on the antioxidant system and the process of colon carcinogenesis, thereby suppressing the development of preneoplastic lesions.
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PMID:A probiotic strain of Bacillus polyfermenticus reduces DMH induced precancerous lesions in F344 male rat. 1732 58

We have established a two-stage, medium-term rat colorectal carcinogenesis model featuring induction of neoplastic lesions within ten weeks. In the present study, we examined the ability of this model to detect weak modifiers. F344 male rats were given three subcutaneous (sc) injections of 1,2-dimethyl-hydrazine (DMH, 40 mg/kg b.w.) in one week followed by drinking water containing 1% dextran sodium sulfate (DSS) for a second week. One week after this regimen, basal diet alone, or diets containing 10% perilla oil, 10% corn oil, 10% dextrin, or 0.1% indole-3-carbinol (I3C) were supplied. The perilla oil and corn oil groups did not show significant differences in the numbers of aberrant crypt foci (ACF) and incidences or multiplicity of proliferative lesions as compared to the controls at either time point. In the dextrin group, the total number of ACF at week ten was significantly increased. With I3C, the total number of ACF and incidence and multiplicities of adenocarcinomas at week ten and the incidence of invasive tumors at week twenty were significantly increased. These data essentially correspond with earlier reported results, except in the vegetable oil cases. Thus, the system is suitable for detection of colorectal carcinogenesis modifiers with advantages over previous models using ACF alone as end points.
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PMID:A new medium-term rat colorectal bioassay applying neoplastic lesions as end points for detection of carcinogenesis modifiers effects with weak or controversial modifiers. 1834 25

Colon cancer is the third most malignant neoplasm in the world and it remains today an important cause of death, especially in western countries. In this study, we have evaluated the chemopreventive efficacy of morin on tissue lipid peroxidation and antioxidant status, which are used as biomarkers in 1,2-dimethylhydrazine-induced colon carcinogenesis in a rat model. Male Wistar rats were divided into four groups and received high fat diet. Group 1 served as control, groups 2 and 4 were given a daily treatment of morin (50 mg/kg body weight) orally, everyday for a total period of 30 weeks. Groups 3 and 4 were given weekly subcutaneous injections of DMH at a dose of 20 mg/kg body weight in the groin for 15 weeks. Animals were sacrificed at the end of 30 weeks. The liver, intestine, colon and caecum from different groups were subjected to histopathological studies, determination of lipid peroxidation and antioxidant status. Our results showed decreased levels of liver enzymic and non-enzymic antioxidants and increased levels of lipid peroxidation (LPO) products such as tissue thiobarbituricacid substances (TBARS), lipid hydroperoxides (LOOH) and conjugated dienes (CD) in DMH treated rats, which were significantly (P < 0.05) reversed on morin supplementation. Moreover, intestinal, colonic and caecal TBARS, LOOH, CD and also the antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR) and reduced glutathione (GSH) were significantly diminished in DMH treated rats, which were significantly (P < 0.05) elevated on simultaneous morin supplementation. Moreover, enhanced activity of intestinal, colonic and caecal ascorbic acid and alpha-tocopherol levels were also observed in DMH alone treated rats, which were significantly (P < 0.05) reduced on morin supplementation. These results indicate that morin could exert a significant chemopreventive effect on colon carcinogenesis induced by DMH.
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PMID:Effect of morin on tissue lipid peroxidation and antioxidant status in 1, 2-dimethylhydrazine induced experimental colon carcinogenesis. 1849 50

The mushroom Agaricus blazei (Ab) has been widely used in folk medicine to treat various diseases including cancer. No information is available on its possible protective effects on the development of colon cancer. The potential blocking effect of Ab intake on the initiation stage of colon carcinogenesis was investigated in a short-term (4-week) bioassay using aberrant crypt foci (ACF) as biomarker. Male Wistar rats were given four subcutaneous injections of the carcinogen 1,2-dimethylhydrazine (DMH, 40 mg/kg bw, twice a week), during 2 weeks to induce ACF. The diet containing Ab at 5% was given 2 weeks before and during carcinogen treatment to investigate the potential beneficial effects of this edible mushroom on DMH-induced ACF. All groups were killed at the end of the fourth week. The colons were analyzed for ACF formation in 1% methylene blue whole-mount preparations and for cell proliferation in histological sections immunohistochemically stained for the proliferating cell nuclear antigen (PCNA). All DMH-treated rats developed ACF mainly in the middle and distal colon. Agaricus blazei intake at 5% did not alter the number of ACF induced by DMH or the PCNA indices in the colonic mucosa. Thus, the results of the present study did not confirm a chemopreventive activity of Ab on the initiation stage of rat colon carcinogenesis.
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PMID:Lack of chemoprevention of dietary Agaricus blazei against rat colonic aberrant crypt foci. 1878 4

We determined the effect of long-term aerobic swimming training regimens of different intensities on colonic carcinogenesis in rats. Male Wistar rats (11 weeks old) were given 4 subcutaneous injections (40 mg/kg body weight each) of 1,2-dimethyl-hydrazine (DMH, dissolved in 0.9% NaCl containing 1.5% EDTA, pH 6.5), at 3-day intervals and divided into three exercise groups that swam with 0% body weight (EG1, N = 11), 2% body weight (EG2, N = 11), and 4% body weight of load (EG3, N = 10), 20 min/day, 5 days/week for 35 weeks, and one sedentary control group (CG, N = 10). At sacrifice, the colon was removed and counted for tumors and aberrant crypt foci. Tumor size was measured and intra-abdominal fat was weighed. The mean number of aberrant crypt foci was reduced only for EG2 compared to CG (26.21 +/- 2.99 vs 36.40 +/- 1.53 crypts; P < 0.05). Tumor incidence was not significantly different among groups (CG: 90%; EG1: 72.7%; EG2: 90%; EG3: 80%). Swimming training did not affect either tumor multiplicity (CG: 2.30 +/- 0.58; EG1: 2.09 +/- 0.44; EG2: 1.27 +/- 0.19; EG3: 1.50 +/- 0.48 tumors) or size (CG: 1.78 +/- 0.24; EG1: 1.81 +/- 0.14; EG2: 1.55 +/- 0.21; EG3: 2.17 +/- 0.22 cm(3)). Intra-abdominal fat was not significantly different among groups (CG: 10.54 +/- 2.73; EG1: 6.12 +/- 1.15; EG2: 7.85 +/- 1.24; EG3: 5.11 +/- 0.74 g). Aerobic swimming training with 2% body weight of load protected against the DMH-induced preneoplastic colon lesions, but not against tumor development in the rat.
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PMID:Long-term aerobic swimming training by rats reduces the number of aberrant crypt foci in 1,2-dimethylhydrazine-induced colon cancer. 1909 53

Epigenome modifications of the human genome play an important role in gene expression regulation and chromatin structure formation. Methylation of cytosine of the CpG dinucleotides is one of the main epigenone modifications of the human genome. Changes in the CpG-islands methylation status of tumor-suppressing genes and oncogenes play an important role in carcinogenesis. Determination of DNA methylation status in oncology is important for early tumor diagnostics, choice and monitoring of cancer treatment and prognosis of survival of patients with cancer after surgeries. There is a wide range of approaches to determination of DNA methylation status now. The review purpose is to characterize main approaches to the determination of the CpG dinucleotides methylation status, which could be used in oncology. They include: bisulfite sequencing, bisulfite pyrosequencing, MS-REA (methylation-sensitive restriction endonuclease assay), MSP (methylation-specific PCR), COBRA (combined bisulfite restriction analysis), MS-SnuPE (methylation-sensitive single nucleotide primer extension), MS-SSCA (methylation-sensitive single-strand conformation analysis), MethyLight, HeavyMethyl, MALDI-TOF MS (matrix-assisted laser desorption/ionization time-to-flight mass spectrometry), FMCA (fluorescence melting curve analysis), restriction genome scanning, use of microarrays for determining genes with increased expression after DNA methylation inhibition, DMH (differential methylation hybridization), use of capability of methylCpG-binding domain of MeCP2 protein to bind methylated DNA, immunoprecipitation of methylated DNA with antibodies specific for methylated cytosines. A general principle, advantages, disadvantages and potential artifacts here been described for each approach in the paper.
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PMID:[Modern methodical approaches to determining the DNA methylation status and their use in oncology]. 1914 Apr 45

The objective of this study was to investigate the chemopreventive potentials of glycine- and proline-rich glycoprotein (SNL glycoprotein, 150-kDa) isolated from Solanum nigrum Linne on formation of colonic aberrant crypt foci (ACF) induced by 1,2-dimethylhydrazine (DMH, 20 mg/kg) in A/J mice. Administration of SNL glycoprotein inhibited phosphorylation of extracellular signal-regulated kinase (ERK), expression of colonic proliferating cell nuclear antigen (PCNA), and frequency of colonic ACF in DMH-stimulated mice colon carcinogenesis. In addition, SNL glycoprotein increased expression of cyclin-dependent kinase inhibitors (p21(WAF/Cip1) and p27(Kip1)), whereas reduced expression of precursor form of apoptosis-related proteins [pro-caspase-3 and pro-poly(ADP-ribose)polymerase (PARP)] in the mice. Interestingly, the results in this study revealed that SNL glycoprotein has suppressive effects on activity of nuclear factor-kappa B (NF-kappaB), whereas it has stimulatory effect on the expression of p53, accompanying inhibitory effects on expression of NF-kappaBp50, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha in DMH-stimulated ACF formation. Also, SNL glycoprotein has inhibitory effects on the formation of thiobarbituric acid reactive substances (TBARS), on the production of inducible nitric oxide (NO), and on the release of lactate dehydrogenase (LDH) in the mice plasma. Collectively, our findings in this study suggest that SNL glycoprotein has chemopreventive activity via modulation of cell proliferation and apoptosis in DMH-treated A/J mice.
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PMID:Glycine- and proline-rich glycoprotein regulates the balance between cell proliferation and apoptosis for ACF formation in 1,2-dimethylhydrazine-treated A/J mice. 1918 65


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