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PubMedDate not supplied

Growth stimulating activity of lung extract on lung-colonizing colon 26 clones and its partial characterization.

The effects of lung tissue extract on the cell growth of eight colon 26 tumor clones, four highly and four poorly lung-colonizing clones, were examined in vitro. Addition of lung extract to serum-free medium stimulated the growth of all four of the highly lung-colonizing clones and one of the poorly lung-colonizing clones, but it had minimal effect on the other three poorly lung-colonizing clones. These results indicate that the lung extract contains a growth stimulating activity; it selectively stimulated some of the colon 26 clones including highly lung-colonizing ones. The growth stimulating activity was not dialyzable, was partially destroyed by heating at 56 degrees C or 80 degrees C for 30 min and completely destroyed by trypsin. These results suggest that the activity resides in a protein. Gel filtration chromatography of lung extract on Sephacryl S-200 revealed that the active component was eluted in a molecular weight range of 90,000-120,000.

Animals↗
PubMed1994

Current follow-up strategies after resection of colon cancer. Results of a survey of members of the American Society of Colon and Rectal Surgeons.

UNLABELLED: The follow-up of patients after potentially curative resection of colon cancer has important clinical and financial implications for patients and society, yet the ideal surveillance strategy is unknown. PURPOSE: The aim of this study was to determine the current follow-up practice pattern of a large, diverse group of experts. METHODS: The 1,663 members of The American Society of Colon and Rectal Surgeons were asked, via a detailed questionnaire, how often they request nine discrete follow-up evaluations in their patients treated for cure with TNM Stage I, II, or III colon cancer over the first five posttreatment years. These evaluations were clinic visit, complete blood count, liver function tests, serum carcinoembryonic antigen (CEA) level, chest x-ray, bone scan, computerized tomographic scan, colonoscopy, and sigmoidoscopy. RESULTS: Forty-six percent (757/1663) completed the survey and 39 percent (646/1663) provided evaluable data. The results indicate that members of The American Society of Colon and Rectal Surgeons generally conduct follow-up on their patients personally after performing colon cancer surgery (rather than sending them back to their referral source). Routine clinic visits and CEA levels are the most frequently performed items for each of the five years. The large majority (> 75 percent) of surgeons see their patients every 3 to 6 months for years 1 and 2, then every 6 to 12 months for years 3, 4, and 5. Approximately 80 percent of respondents obtain CEA levels every 3 to 6 months for years 1, 2, and 3, and every 6 to 12 months for years 4 and 5. Colonoscopy is performed annually by 46 to 70 percent of respondents, depending on year. A chest x-ray is obtained yearly by 46 to 56 percent, depending on year. The majority of the members of The American Society of Colon and Rectal Surgeons do not routinely request computerized tomographic scan or bone scan at any time. There is great variation in the pattern of use of complete blood count and liver function tests. Members of The American Society of Colon and Rectal Surgeons from the United States tend to follow their patients more closely than do those living in other countries. The intensity of follow-up does not markedly vary across TNM Stages I to III. CONCLUSION: The surveillance strategies reported here rely most heavily on clinic visits and CEA level determinations, generally reflecting guidelines previously proposed in the current literature.

Appointments and Schedules↗
PubMed1995

Impact of family history of colon cancer on development of multiple primaries after diagnosis of colon cancer.

PURPOSE: The purpose of this study was to assess risk of developing multiple primaries after a diagnosis of colon cancer and to determine the impact that having a family history of cancer has on cancer risk. METHODS: Data from the Utah Cancer Registry and the Utah Population Database were used. A cohort of 2,236 first primary colon cancers were observed for the subsequent development of additional primary cancers. RESULTS: We observed a greater than expected incidence of colon, rectal, and pancreatic cancers among the cohort. The standardized incidence ratios were 2.77 (95 percent confidence interval (CI), 2.07-3.70), 2.26 (95 percent CI, 1.34-3.81), and 2.38 (95 percent CI, 1.32-4.30), respectively. Having a family history of colon or rectal cancer did not greatly influence risk of having a multiple primary. However, there was a trend toward increased risk of pancreatic cancer (hazard rate ratios, 1.99; 95 percent CI, 0.67-5.90) and bladder cancer (hazard rate ratios, 2.35; 95 percent CI, 0.77-7.18) among patients with a family history of rectal cancer. We also observed that risk of uterine cancer in the cohort was positively associated with family history of uterine cancer, risk of breast cancer was positively associated with family history of breast cancer, and risk of prostate cancer was positively associated with family history of prostate cancer. CONCLUSIONS: People with colon cancer are at a greater risk of developing colon, rectal, and possibly pancreatic cancer. Although a family history of colon or rectal cancer did not have a large impact on developing other cancers, a family history of other primary cancers did influence risk of other cancers.

Aged↗
PubMed2004

Multidetector-row CT findings of colonic perforation: direct visualization of ruptured colonic wall.

BACKGROUND: We examined the findings of contrast-enhanced multidetector-row computed tomography (MD-CT) in patients with colonic perforation. METHODS: Abdominal contrast-enhanced MD-CT findings in six patients with colonic perforation were reviewed retrospectively. Patients (three men and three women) were 74 to 88 years old (mean age = 78 years). Colonic perforation was confirmed by surgery. CT findings were correlated with surgical and pathologic findings. RESULT: The site of colonic perforation was suggested by the following combination of CT findings: free air, dirty mass, dirty fat sign, extraluminal fluid collection, bowel wall thickening, and interruption of colonic wall. The ruptured colonic wall was directly visualized in four cases (67%). CONCLUSION: Abdominal contrast-enhanced MD-CT may improve the accuracy of diagnosis and localization of colonic perforation.

Aged↗
PubMed2005

Functional expression of the interleukin-11 receptor alpha-chain in normal colonic epithelium and colon cancer.

BACKGROUND: Interleukin-11 (IL-11) has been evaluated as an anti-inflammatory and mucosa-protective therapeutic agent in inflammatory bowel diseases (IBDs). Activity of IL-11 requires binding to the alpha receptor subunit (IL-11Ralpha) that provides ligand specificity. Recently, we showed that in the intestinal mucosa, IL-11Ralpha is mainly present on epithelial cells mediating antiapoptotic effects. The aim of this study was to investigate the expression profiling of IL-11Ralpha and its downstream signaling cascade in colonic adenoma and carcinoma. MATERIALS AND METHODS: The expression of IL-11Ralpha in normal colonic mucosa, 11 colonic adenomas, and 10 carcinomas was analyzed by immunohistochemistry. In addition, IL-11Ralpha-expression and IL-11Ralpha-induced phosphorylation of signal transducer and activator of transcription (STAT)3 were investigated by Western blot analysis. RESULTS: Immunohistochemistry revealed significant IL-11-Ralpha expression in epithelial cells of normal colonic mucosa. In contrast, the expression of IL-11-Ralpha in colon adenomas and carcinomas was either absent or only detectable in very few scattered epithelial cells. Densitometric analysis of Western blots confirmed these results, showing a decrease of IL-11Ralpha-protein in cells isolated from adenomas or carcinomas. Reduced STAT3-phosphorylation in carcinoma cells indicated functional consequences of decreased IL-11Ralpha-protein expression on signal transduction. CONCLUSION: This study demonstrates a decrease of IL-11-Ralpha-protein expression in epithelial cells isolated from colon carcinomas and adenomas compared to normal colonic mucosa and a reduced STAT3 signaling. Because of reduced binding and signal transduction, it is unlikely that therapeutically administered IL-11 would contribute to colorectal carcinoma induction and growth.

Adult↗
PubMed2000

The effect of intraoperative colonic lavage with NG-nitro-L-arginine methyl ester (L-NAME) on anastomotic healing in the presence of left-sided colonic obstruction in the rat.

The effect of intraoperative colonic lavage with NG-nitro-L-arginine methyl ester (L-NAME) on the healing of colonic anastomosis in the presence of a left-sided obstruction in the rat was investigated. Left-sided colonic obstruction was created in 144 Wistar rats. The obstruction site was excised 24h later and anastomosis was performed after either no irrigation or colonic lavage with either saline, povidone iodine (PI), short-chain fatty acids (SCFA), L-NAME, or glutamine, in 24 animals each. Animals were killed on days 3 and 6, and a 4-cm colonic segment with the anastomosis at the center was excised. Bursting pressure (BP) and hydroxyproline (HP) content were measured. In the saline, PI, and SCFA groups, BP was higher (P < 0.05, P < 0.05, and P < 0.001, respectively) and HP concentration was similar compared with controls. Both the BP and HP concentrations were higher in the glutamine group compared with controls (P < 0.001). BP was lower (P < 0.05) and HP concentration was similar in the L-NAME group compared with the control group. Colonocyte nutrition and tissue perfusion are the mainstays of anastomotic healing. Intraoperative colonic lavage with L-NAME suppresses colonic anastomotic healing in the presence of a left-sided obstruction.

Anastomosis, Surgical↗
PubMed2002

Neorectal reservoir is not the functional principle of the colonic J-pouch: the volume of a short colonic J-pouch does not differ from a straight coloanal anastomosis.

BACKGROUND: Low anterior resection with coloanal anastomosis prevents a definitive stoma in patients with distal rectal cancer. However, imperative stool urge, stool fragmentation, prolonged stooling sessions, and minor problems of incontinence are frequently observed in the postoperative situation and negatively affect quality of life. Therefore, the colonic J-pouch was originally constructed to create a stool reservoir. In a randomized, prospective study, the short (5 cm) colonic J-pouch was tested for function and continence vs. straight coloanal anastomosis. METHODS: Over a period of 30 months, 74 consecutive patients (55 males) with rectal cancer in the lower and middle third of the rectum were included and randomized into two groups. Anastomosis was performed either as a coloanal or a colon-pouch-anal anastomosis. The standardized surgical procedure included mobilization of the left hemicolon, central ligation of the inferior mesenteric artery and vein, preaortal lymph node dissection, autonomic nerve preservation, and total mesorectal excision. The anastomosis was performed at the upper anal canal or at the intersphincteric level. All patients were evaluated preoperatively and six months postoperatively for fecal continence, including sphincter manometry and defecation habits. In addition, quality of life was determined by use of a standardized questionnaire (European Organization for Research and Treatment of Cancer, EORTC-QLQ-C30). RESULTS: Thirty-seven patients were randomized into each group. In general, problems with continence for liquids or gas occurred less frequently in the colonic J-pouch group 6 months after surgery. The frequency of bowel movements was lower in the J-pouch group (2.5 per day) than in the coloanal group (4.7 per day). Importantly, in a manometric study at the same postoperative point, neorectal capacity was decreased to a similar degree in both groups compared with the preoperative rectal volume. Thus, the expected and postulated reservoir effect could not be achieved by forming a 5-cm colonic J-pouch. CONCLUSION: The colonic J-pouch was superior with regard to continence for gas and liquids compared with a straight coloanal anastomosis. Furthermore, stool frequency was significantly lower in the J-pouch group than in the coloanal reconstruction group. However, because neorectal capacity decreased equally in both groups, we speculate that the advantage of the colonic J-pouch is not in the creation of a larger neorectal reservoir but rather may be related to decreased motility.

Adult↗
PubMed2006

Induction and recovery of colonic motility/defecatory disorders after extrinsic denervation of the colon and rectum in rats.

BACKGROUND: Anterior resection for rectal disease is associated with extrinsic autonomic denervation of the neorectum, which may influence the myenteric plexus, and subsequently the motility/defecatory status after operation. METHODS: A rat model with denervated neorectum was constructed. Colonic contractile activity in vivo, the amount of generic neuron marker (PGP 9.5) and nitric oxide synthase (NOS) were measured periodically. The responses of the muscle strip in each period to electrical field stimulation were evaluated using various neurotransmitters. RESULTS: In rats with denervated neorectum, giant migrating contractions (GMCs) of the distal colon, the number of fecal lumps per day and their small size, significantly increased in the early phase postoperatively, although both recovered in the late-phase period. The contractile response of the muscle strip of the denervated colon to acetylcholine was reduced throughout the period; however, contraction of the denervated colon under the addition of NO inhibitor (l-NAME) was enhanced significantly in the late-phase period, and recovered to the control level by atropine. Neuronal NOS, but not PGP 9.5 concentration, in the myenteric plexus at the distal denervated colon, significantly increased in the late-phase period. None of the above items differed from the control at other colonic portions throughout the period. CONCLUSIONS: Extrinsic autonomic denervation causes abnormal hyper-motility in the neorectum, which may be associated with multiple evacuations in the early phase postoperatively. Increased acetylcholine and the subsequent increase of neuronal NOS in the myenteric plexus may be an adaptive mechanism to compensate for such abnormal colonic motility after extrinsic denervation.

Animals↗
PubMed2001

Effects of purified green and black tea polyphenols on cyclooxygenase- and lipoxygenase-dependent metabolism of arachidonic acid in human colon mucosa and colon tumor tissues.

The effects of green and black tea polyphenols on cyclooxygenase (COX)- and lipoxygenase (LOX)-dependent arachidonic acid metabolism in normal human colon mucosa and colon cancers were investigated. At a concentration of 30 microg/mL, (-)-epigallocatechin-3-gallate (EGCG), (-)-epigallocatechin (EGC), and (-)-epicatechin-3-gallate (ECG) from green tea and theaflavins from black tea inhibited LOX-dependent activity by 30-75%. The formation of 5-, 12-, and 15-LOX metabolites was inhibited to a similar extent. Tea polyphenols also inhibited COX-dependent arachidonic acid metabolism in microsomes from normal colon mucosa, with ECG showing the strongest inhibition. The formation of thromboxane (TBX) and 12-hydroxyheptadecatrienoic acid (HHT) was decreased to a greater extent than other metabolites. The inhibitory effects of tea polyphenols on COX activity, however, were less pronounced in tumor microsomes than in normal colon mucosal microsomes. Theaflavins strongly inhibited the formation of TBX and HHT, but increased the production of prostaglandin E(2) (PGE(2)) in tumor microsomes. The enhancing effect of theaflavins on PGE(2) production was related to the COX-2 level in the microsomes. Although theaflavin inhibited ovine COX-2, its activity in the formation of PGE(2) was stimulated by theaflavin when ovine COX-2 was mixed with microsomes, suggesting that theaflavin affects the interaction of COX-2 with other microsomal factors (e.g. PGE synthase). The present results indicate that tea polyphenols can affect arachidonic acid metabolism in human colon mucosa and colon tumors, and this action may alter the risk for colon cancer in humans.

Antioxidants↗
PubMed1983

Colon interposition or gastric tube? Follow-up study of colon-esophagus and gastric tube-esophagus patients.

Between 1963 and 1980, 34 elective esophageal reconstructions were performed on 29 esophageal atresia patients. Five patients needed two reconstructions. Among 20 colon replacement procedures there were 2 early deaths and three transplants failed. In 14 gastric tube reconstructions there was no mortality, but two tubes failed. The mean follow-up age of the 15 colon esophagus patients was 11.8 yrs, while for the 12 gastric tube patients it was 5.6 yrs. One death occurred during the follow-up period in each group. Late complications occurred in 7/15 of the colon and 3/12 of the gastric tube groups. Most of the serious complications occurred within 3 yr after surgery. The previously reported malabsorption following colon interposition seemed to be transient. At follow-up all but 3 patients with no significant other anomalies were within two standard deviations of the mean of height and weight. All were satisfied with their new esophagus. Nine out of 14 of the colon and 7/11 of the gastric tube groups were without symptoms, the others having only minor complaints. It is concluded that both colon replacement and gastric tube are satisfactory methods for esophageal reconstruction, and the long-term function seems equally good. However, the gastric tube procedure is easier to perform, has less mortality and fewer complications than colon replacement.

Body Height↗
PubMed1998

Colonic histopathology in untreated celiac sprue or refractory sprue: is it lymphocytic colitis or colonic lymphocytosis?

Colonic histopathology in some patients with untreated celiac sprue and refractory sprue has been said to be indistinguishable from lymphocytic colitis, but there have been no objective comparisons on which this is based. The purpose of this study was to determine the prevalence and to characterize the nature of colonic histopathology at the time of diagnosis in patients with celiac or refractory sprue. Colonoscopic biopsy specimens obtained at the time of diagnosis from 16 patients with celiac sprue, six patients with refractory sprue, nine patients with lymphocytic colitis, and five normal controls were analyzed blindly by histological and morphometric methods, quantitating the number and specific subtypes of inflammatory cells within the lamina propria and epithelium. Immunoperoxidase staining of intraepithelial lymphocytes with a monoclonal antibody to CD8 also was performed. Three of 16 patients with untreated celiac sprue (19%) were thought to have colonic histological abnormalities, which by morphometry consisted of slightly increased numbers of lymphocytes in the surface epithelium and lamina propria, many of which were CD8-positive. These abnormalities were distinguishable from lymphocytic colitis by the lack of increased overall lamina propria cellularity and surface epithelial abnormalities, and by fewer intraepithelial lymphocytes. In refractory sprue, colonic histological abnormalities were more frequent than in celiac sprue, occurring in four of six patients (67%), more pronounced, and identical to those in the lymphocytic colitis syndrome. However, colonic intraepithelial lymphocytes in lymphocytic colitis were mostly CD8-positive, whereas those in the colitis of refractory sprue rarely were. Mild colonic lymphocytosis in patients with untreated celiac sprue should be distinguished from lymphocytic colitis by the lack of surface epithelial abnormalities, the lack of increased cellularity of the lamina propria, and the lack of ongoing watery diarrhea after treatment with a gluten-free diet. In contrast, colonic histopathology in refractory sprue is indistinguishable from lymphocytic colitis, although immunohistochemical differences do exist.

Adolescent↗
PubMed1999

The peptide content of colonic afferents decreases following colonic inflammation.

Peripheral injury produces long term changes in peptide content in dorsal root ganglion (DRG) cells that contribute to the inflammatory process in the periphery and neuronal plasticity in the spinal cord. We report here the proportion of colonic afferents labeled for calcitonin gene-related peptide (CGRP), substance P (SP) or somatostatin (Som) in the T13-L2 and L6-S2 DRG and changes in the percentage of SP or CGRP labeled afferents 6, 24, and 72 h following induction of experimental colitis. Following injection of fluorogold (FG) into the descending colon, significantly more FG labeled DRG cells were observed in the T13-L2 than L6-S2 DRG. In noninflamed rats, in both spinal regions, 60-70% of the colonic afferents that were labeled with FG were double labeled for SP. Similar results were obtained when double labeling for CGRP. Only 20-30% of the FG labeled afferents were double labeled for Som. Following experimental colitis induced by intracolonic zymosan, there was a significant decrease in the percentage of cells double labeled for SP in the T13-L2 and L6-S2 DRG at 6, 24, and 72 h. The percentage of CGRP double labeled cells was decreased in the T13-L2 DRG at all time points, but only at 24 h in the L6-S2 DRG. The cell bodies of CGRP labeled colonic afferents were significantly larger than SP or Som in control rats. Inflammation did not affect the mean size of the double labeled cells. These results suggest that colonic inflammation increases SP and CGRP release in the spinal cord and the colon that is manifest as a decrease in peptide content in the cell bodies of the colonic afferents during the first 72 h following injury.

Abdominal Pain↗
PubMed2000

Colon cancer screening, lifestyle, and risk of colon cancer.

OBJECTIVES: Sigmoidoscopy screening and fecal occult blood (FOB) tests have been demonstrated as effective ways to reduce mortality from colorectal cancer. However, most studies of colorectal cancer screening and cancer mortality have not taken into consideration lifestyle factors that could account for the observed associations. The purpose of this study was to determine the association between screening and incidence of colon cancer, taking into consideration important lifestyle factors. METHODS: We estimated the association between screening and colon cancer after taking into consideration health and lifestyle factors using data obtained as part of population-based case-control study of incident colon cancers. RESULTS: Sigmoidoscopy screening, especially as part of a checkup, was protective against incident colon cancer in both men (OR 0.56, 95% CI 0.44-0.77) and women (OR 0.53, 95% CI 0.33-0.77) after adjusting for other risk factors for colon cancer. For men, associations were stronger for distal tumors (OR 0.48, 95% CI 0.31-0.71) than for proximal tumors (OR 0.67, 95% CI 0.45-1.11). We did not observe significant associations between FOB test and colon cancer. Differences in characteristics between those who were screened and not screened were also observed. Men were more likely to report having a sigmoidoscopy as part of a checkup than were women, as were people with higher levels of education. People who reported having a sigmoidoscopy as part of a checkup also reported eating diets lower in fat and higher in fiber, folate, and vegetables. Men were more likely to report higher levels of physical activity, and women were more likely to report taking hormone replacement therapy (HRT) if they also reported a sigmoidoscopy. Both men and women who reported a sigmoidoscopy for screening purposes were more likely to have a family history of colorectal cancer. CONCLUSIONS: These data provide additional support for the benefits of having a screening sigmoidoscopy. The associations between screening sigmoidoscopy and colon cancer do not appear to be the result of lifestyle factors.

Aged↗
PubMed2004

Lipopolysaccharide induces CD25-positive, IL-10-producing lymphocytes without secretion of proinflammatory cytokines in the human colon: low MD-2 mRNA expression in colonic macrophages.

Despite the huge number of colonized Gram-negative bacteria in the colon, the normal colon maintains its homeostasis without any excessive immune response. To investigate the potential mechanisms involved, human colonic lamina propria mononuclear cells (LPMCs) obtained from uninflamed mucosa were cultured with lipopolysaccharide (LPS) prepared from Bacteroides vulgatus (BV-LPS) or Bacteroides fragilis (BF-LPS), as representatives of indigenous flora, or pathogenic Salmonella minnesota (SM-LPS). Colonic LPMCs failed to produce inflammatory cytokines in response to any type of LPS. Colonic macrophages barely expressed mRNA for MD-2, an essential association molecule for LPS signaling via Toll-like receptor 4. Further, BV-LPS induced CD25 and Foxp3 expression in lymphocytes and CD4(+)CD25(+) cells expressed IL-10 mRNA. Thus, the low expression of functioning LPS receptor molecules and induction of IL-10-producing CD4(+)CD25(+) lymphocytes by indigenous LPS may play a central role in the maintenance of colonic immunological homeostasis.

Aged↗
PubMed2000

Utilization of short-chain fatty acids by colonic mucosal tissue strips. A new method of assessing colonic mucosal metabolism.

BACKGROUND: Previous metabolic studies of the colonic mucosa have been done using isolated cells or small biopsy specimens. METHODS: A new method for assessing the utilization of short-chain fatty acids in human colonic mucosal tissue strips considerably larger than routine samples was evaluated and compared with the method of isolated colonocytes. Human colonic mucosal strips and isolated human and rat colonocytes were incubated with acetate (C2), butyrate (C4), and hexanoate (C6), and oxidation rates obtained by quantifying the production of CO2. RESULTS: The wet weight of strips was highly correlated with the production of CO2, and intersample coefficient of variance was <10%. The production of CO2 from the oxidation of C2, C4, and C6 was in the order of C2 > C4 > C6 for both strips and isolated human and rat colonocytes. The production of adenosine triphosphate (ATP) in strips and isolated human and rat colonocytes was in the order of C2 < or = C4 < or = C6. The Km value for the oxidation of butyrate to CO2 in strips (1.8 mmol/l) was several times higher than previously reported for isolated human and rat colonocytes (0.1-0.3 mmol/l). CONCLUSIONS: This new method is highly reproducible and able to assess the metabolic activity of the colonic mucosa. The high Km value of butyrate oxidation in mucosal strips seems to reflect the in vivo Km value of colonocytes and shows the importance of a preserved anatomic structure in metabolic studies of the colonic epithelium. The low Km value for isolated colonocytes probably reflects the intracellular ability to oxidize butyrate. We propose that both isolated colonocytes and mucosal strips be used in studies of colonic mucosal metabolism. This method is relevant in disease states of the colon in which a disagreement prevails as to the ability to oxidize butyrate by colonocytes, such as in ulcerative colitis.

Acetates↗
PubMed1991

Modulating effects of calcium in animal models of colon carcinogenesis and short-term studies in subjects at increased risk for colon cancer.

A substantive amount of evidence from animal models supports the hypothesis that dietary fat is an etiological factor in colon cancer. Although various theories account for possible mechanisms, it is clear that under the influence of a basic colonic pH, fatty acids and bile acids may become highly surfactant in the colon, causing cell loss and compensatory hyperproliferation. Calcium likely reduces lipid damage in the colon by complexing with fat to form mineral-fat complexes or soaps. It has been shown in an increasing number of animal experiments that calcium has the ability to inhibit colon cancer. In limited studies in man, the colonic hyperproliferation associated with increased risk for colon cancer has been reversed for short periods by administration of supplemental dietary calcium. Taken together the available evidence suggests that increases in the daily intake of calcium in the diet may provide a means of colorectal-cancer control.

Animals↗
PubMed1995

Moderate folate deficiency does not cause global hypomethylation of hepatic and colonic DNA or c-myc-specific hypomethylation of colonic DNA in rats.

Global and gene-specific DNA hypomethylation is considered to be an important early epigenetic event in several human neoplasms. A growing body of evidence has suggested that DNA methylation can be altered by dietary manipulation of methyl group donors. This study investigated whether moderate depletion of folate, a dietary component needed for the synthesis of methyl groups, would cause decreased hepatic and colonic S-adenosylmethionine concentrations, and thereby lead to global and/or protooncogene-specific DNA hypomethylation. Weanling rats were fed an amino acid-defined diet containing either 0 or 8 mg folate/kg diet for 15 or 24 wk. Significantly lower systemic, hepatic and colonic folate concentrations were observed in the moderately folate-depleted rats than in controls at both 15 and 24 wk (P < 0.005). Although hepatic S-adenosylmethionine was significantly lower in the moderately folate-depleted rats than in controls at the two time points (P < 0.03), colonic S-adenosylmethionine concentrations were not significantly different between the two groups at either time point. No significant differences between the folate-depleted and control animals could be detected with regard to global DNA methylation in the liver or colonic mucosa. Furthermore, c-myc protooncogene-specific DNA methylation in the colonic mucosa was not significantly different between these two groups of animals. These results indicate that moderate folate depletion does not cause a significant reduction in global DNA methylation in liver or colonic mucosa or in c-myc-specific colonic mucosal DNA methylation in this rat model.

Animals↗
PubMed1997

Bifidobacterium longum, a lactic acid-producing intestinal bacterium inhibits colon cancer and modulates the intermediate biomarkers of colon carcinogenesis.

The human colon can be described as a complex microbial ecosystem, comprising several hundred bacterial species. Some of these enteric bacteria are beneficial to the host and have been shown to exert antimutagenic and anticarcinogenic properties. We have investigated the colon tumor inhibitory activity of Bifidobacterium longum, a lactic acid-producing enterobacterium. The modifying effects of this lactic culture on colonic mucosal and/or tumor cell proliferation, ODC activity and ras-p21 oncoprotein expression in colon carcinogenesis were also analyzed. Male F344 rats were fed a modified AIN-76A diet containing 0 or 2% lyophilized cultures of B. longum and s.c. administered azoxymethane (AOM) dissolved in normal saline at a dose of 15 mg/kg body wt, once weekly for 2 weeks. Vehicle controls received an equal volume of normal saline s.c. Animals were maintained on control or experimental diets until termination of the study. Animals intended for analysis of cell proliferation were killed 20 weeks after the second AOM injection, whereas animals intended for colon tumor analysis and measurement of ODC activity and ras-p21 expression were killed 40 weeks after the last AOM injection. The data demonstrate that dietary administration of lyophilized cultures of B. longum resulted in significant suppression of colon tumor incidence and tumor multiplicity and also reduced tumor volume. Results also revealed that ingestion of B. longum significantly inhibited AOM-induced cell proliferation, ODC activity and expression of ras-p21 oncoprotein. Data suggest that oral administration of probiotic B. longum exerts strong antitumor activity, as indicated by modulation of the intermediate biomarkers of colon cancer, and consequently reduced tumor outcome.

Animals↗