Crypt Column Research Articles

Dietary fibre on cell proliferation in large bowel mucosal crypts near or away from lymphoid nodules and on mineral bioavailability.

The effect of consumption for 24 weeks of different amounts (0%, 5% or 10% w/w) of fermentable (pectin and guar gum) or nonfermentable (cellulose and lignin) dietary fibres on cell proliferation and other parameters in large bowel mucosal crypts was studied in rats. In all 12 dietary groups, the crypts located over the distal aggregate of lymphoid nodules (ALN) had more colchicine arrested metaphase figures per midaxial crypt section (MC) and a longer crypt column height than crypts located three to four cm away from this ALN. These differences are attributed to the tropic influence of nodular cells in the ALN. Consumption of fermentable fibre decreased pH in the lumen of the caecum, and glucose, Zn and Cu in serum but increased Ca and Mg in serum. The decrease in caecal pH and serum glucose was significantly correlated with a decrease in MC. Increased intake of the nonfermentable fibre types increased faecal bulk but had no significant correlation with the other measured crypt parameters. Multiple regression analyses was used to model the relationships between the mucosal crypt criterion variables and the two measured predictor variables, caecal pH and serum glucose. Relationships between dietary fibre, ALN, MC, bioavailability of dietary minerals and risk of colorectal cancer are discussed.

Chemoprevention studies of the flavonoids quercetin and rutin in normal and azoxymethane-treated mouse colon.

In this study we investigated the chemopreventive effects of quercetin and rutin when added to standard AIN-76A diet and fed to normal and azoxymethane (AOM)-treated mice. Early changes in colonic mucosa were analyzed, including colonic cell proliferation, apoptotic cell death, cyclin D(1) expression and focal areas of dysplasia (FAD). The findings show that the number of colonic epithelial cells per crypt column increased (P: < 0.01) in each normal mouse group fed the flavonoids; AOM administration increased colonic crypt cell proliferation and resulted in a marked rise of bromodeoxyuridine-labeled cells in the lower proliferative zone of the crypt. Both supplementary dietary quercetin and rutin increased the apoptotic index and caused a redistribution of apoptotic cells along the crypt axis in normal mice fed a standard AIN-76A diet. The number of apoptotic cells/column and apoptotic indices markedly increased (P: < 0.01) in the AOM-treated group compared with untreated animals; apoptotic cells expanded throughout the colonic crypts after flavonoid supplementation and AOM administration. Positive cyclin D(1) expression was detected in mice on diets supplemented either with quercetin (P: < 0.01) or rutin (P: < 0.05). AOM administration resulted in the formation of FAD. Both the number of mice exhibiting FAD and the total numer of FAD observed were significantly reduced (P: < 0.01) in AOM-treated animals fed flavonoids compared with mice maintained on the standard AIN-76A diet. Surprisingly, however, quercetin alone was able to induce FAD in 22% of normal mice fed the standard AIN-76A diet.

Arabinoxylan Fiber from a By-Product of Wheat Flour Processing Behaves Physiologically like a Soluble, Fermentable Fiber in the Large Bowel of Rats

Arabinoxylan is a major dietary fiber component of many cereals. Its physiological effects in the colon are largely unknown. This study examined the effects of an arabinoxylan-rich fiber (AX) extracted from a by-product of wheat flour processing in the rat colon compared with well-characterized soluble/rapidly fermentable and insoluble/slowly fermentable fibers. Rats were fed diets containing no fiber (NF) or 100 g/kg of total dietary fiber from AX, guar gum (GG) or wheat bran (WB) for 4 wk. Cecal mass and short-chain fatty acid (SCFA) pool were significantly higher while pH was significantly lower in the fiber-supplemented groups, particularly in the AX and GG groups. The pattern of SCFA production in the cecum was altered; AX fiber was a good source for acetate while GG and WB favored propionate and butyrate production, respectively. Fecal output was 7-, 6- and 5-fold higher, respectively, in the AX, GG and WB than in the NF groups (P < 0.01). All epithelial proliferation indices (crypt column height, number of mitotic cells/crypt column and mitotic index) differed significantly across the groups in a descending order of AX > GG > WB > NF. Distal mucosal dipeptidyl peptidase IV activities, which indicate cell differentiation status, were significantly lower in fiber-supplemented groups than in the NF groups. Distal mucosal alkaline phosphatase activities, induced as a response to injury or stress, were significantly higher for the AX and GG groups than for the NF or WB groups (P < 0.001). These results indicate that AX fiber behaves like a rapidly fermentable, soluble fiber in the rat colon.

Blood group antigen expression in the rat colon II. Modulation by dietary ethanol consumption.

In the accompanying article, we established that in the rat distal colon expression of H, B, and Le(b) blood group antigens by goblet cells is phenotypically fetal in nature. Because of the cocarcinogenic property of ethanol, the present study examined the effects of dietary ethanol consumption, fasting, and withdrawal on the expression of these antigens in the adult rat colon. To that effect, male adult Sprague-Dawley rats were pair-fed ethanol-containing or control Lieber-DeCarli liquid diets for 3 weeks. The effects of ethanol withdrawal were studied in rats fed the ethanol-containing diet for 3 weeks followed by the control diet for 1, 3, and 6 days. In rats fed the control diet, no antigen expression in the distal colon was observed, as expected. Ethanol feeding for 3 weeks resulted in a striking reappearance of H, B, and Le(b) antigens in goblet cells of the distal colon. In colonic crypts, a lower-to-upper crypt gradient of increasing numbers of positive goblet cells was present, suggesting that the induction of antigen expression paralleled the differentiation of goblet cells. After an overnight fast, the number of positive cells was significantly decreased. Withdrawal of ethanol for 1 day further decreased the number of positive goblet cells. The decrease was reflected by a downward shift in the number of positive cells per crypt column, which was more striking in the lower and mid-crypt segments than in the upper segment, suggesting that antigen expression was more labile in immature differentiating goblet cells than in mature ones. No antigen staining of goblet cells was detected after 3 and 6 days of ethanol withdrawal. Hence, expression of H, B, and Le(b) antigens by goblet cells of the distal colon can be modulated by ethanol consumption. Expression in the distal colon of A and Le(a) antigens, which did not exhibit a fetal phenotype, was not affected by ethanol feeding. In conclusion, because of the oncofetal phenotype of H, B, and Le(b) antigens, their reappearance in the distal colon may serve as a cytochemical marker for early recognition of epithelial changes of the colon in ethanol-related cocarcinogenesis before more overt manifestations of neoplasia.

Effect of butyrate on paracellular permeability in rat distal colonic mucosa ex vivo.

The effects of butyrate on colonic epithelial barrier function are poorly understood. The aim of this study was to examine the short-term effects of butyrate on paracellular permeability of rat distal colonic epithelium. Mucosa mounted in Ussing chambers was treated with butyrate (1-10 mmol/L) for 4 h. Transepithelial conductance, [51Cr]-EDTA flux, mucosal brush border hydrolase activity and epithelial kinetics, using proliferating cell nuclear antigen (PCNA) staining, were measured. On exposure to butyrate (10 mmol/L, but not 1 or 5 mmol/L), transepithelial conductance was 65 +/- 2% higher (mean +/- SEM; n = 8, P < 0.05, paired t-test) and the rate coefficient for [51Cr]-EDTA flux was 65 +/- 25% higher (P = 0.03) than those of control tissue. Histologically, the epithelium exhibited no signs of injury, but butyrate-treated tissue exhibited interstitial oedema consistent with water uptake in association with butyrate absorption. Butyrate caused a reduction in crypt column height to 30.6 +/- 1.6 cells from 33.4 +/- 1.8 cells in controls (n = 10, P < 0.03), but the number of cells per crypt column staining with PCNA was unchanged. Butyrate significantly reduced the mucosal activities of alkaline phosphatase by 40 +/- 16%, maltase by 54 +/- 12% and dipeptidyl peptidase IV by 41 +/- 14%. Acute exposure to butyrate increased paracellular permeability in rat distal colon. The mechanism involved may relate to the loss of differentiated surface epithelial cells, or as a physiological response to Na+-coupled butyrate uptake.

Relationship of hydrolase activities to epithelial cell turnover in distal colonic mucosa of normal rats.

The relationships between changes induced by diet in colonic epithelial kinetics and in the activities of brush border hydrolases are poorly defined. The aims of this study are to define these relationships, as changes in kinetics would be expected to influence differentiation, and to determine whether the type of ingested dietary indigestible carbohydrates influences hydrolase activities. Groups of eight rats were fed a low fibre diet +/- supplements of different types of indigestible carbohydrates for 4 weeks. Alkaline phosphatase (ALP) and dipeptidyl peptidase IV (DPPIV) activities and epithelial kinetics were measured in distal colonic mucosa. Median ALP activities correlated positively and DPPIV activity negatively with the median proportion of cells entering metaphase (r = 0.58 and -0.58, respectively; P < 0.05) and number of metaphase arrests per crypt column across the diets (r = 0.59 and 0.58, respectively; P < 0.05). Stepwise regression analysis showed that both hydrolases independently predicted these kinetic indices (R2 > 63% for each). Mucosal ALP activities were markedly elevated during consumption of raw potato starch, guar gum and methylcellulose, while only potato starch caused a significant elevation of DPPIV activities. The type of indigestible carbohydrate in the diet influences colonic mucosal hydrolase activities. The opposite relationship between kinetics and each of the two hydrolases indicates that these hydrolases do not reflect the same event; dipeptidyl peptidase IV might relate to differentiation status while ALP could also be influenced by epithelial irritation due to changes in luminal conditions.

Cell proliferation, differentiation, and apoptosis are modified by n-3 polyunsaturated fatty acids in normal colonic mucosa.

Supplementation with low doses of eicosapentaenoic (EPA) or docosahexaenoic (DHA) acid was used here to investigate changes in epithelial proliferation, differentiation, and apoptosis in normal rat colonic mucosa. ACI/T rats received by oral administration low doses of purified EPA or DHA ethyl esters (1 g/kg body weight) and colonic mucosa was analyzed for cell proliferation, differentiation, and apoptosis. n-3 Polyunsaturated fatty acid incorporation into membrane phospholipids was investigated as reflections of fatty acid metabolism. Both EPA and DHA suppressed colonocyte proliferation and increased the numbers of differentiating and apoptotic cells without modification of the crypt morphology and the number of cells per crypt columns. A significant incorporation of the supplemented fatty acids into total phospholipids was observed. This enrichment was accompanied by a decreased content in arachidonic acid. The observation that EPA and DHA do not alter crypt morphology although they modify cell turnover in normal colonic mucosa suggests a possible use of these fatty acids as dietary chemopreventive agents.

Urokinase and the intestinal mucosa: evidence for a role in epithelial cell turnover

Background—The functions of urokinase in intestinal epithelia are unknown.Aims—To determine the relation of urokinase expressed by intestinal epithelial cells to their position in the crypt-villus/surface axis and of mucosal urokinase...

Proliferation of goblet cells and vacuolated cells in the rabbit distal colon.

Previous studies of colonic epithelial cell kinetics in mice and rats revealed a pattern similar to small intestine, where basally located stem cells proliferate, differentiating as they migrate towards the surface epithelium. Vacuolated and goblet cells are assumed to co-migrate at the same rate. The present study indicates that rabbit distal colon has more complicated epithelial cell kinetics. The zone of proliferation was detected immunohistochemically using proliferating cell nuclear antigen (PCNA) and confirmed with the use of colchicine to arrest dividing cells in metaphase. Migrating cells were tracked from the zero-hour position (PCNA labeling, mitosis) to positions 24, 48, 72 hrs by monitoring cell migration with the thymidine analog 5-Bromo-2-Deoxyuridine (BrdU). PCNA revealed a major proliferative zone in the upper third of the crypt column and the presence of mitotic figures after colchicine corroborated these results. Differentiated vacuolated cell proliferation was detected at three crypt sites: base, middle, and top of the crypt, while columnar cells arose from a population of dividing cells at the top of the crypt. Turnover of columnar and vacuolated cells occurred within 72 hrs. Goblet cells exhibited maximal proliferation at the crypt base and migrated at a much slower rate than the other cell types. In rabbit distal colon, populations of proliferating cells exist at multiple levels of the crypt column. Vacuolated and goblet cells differ in their labeling indices and migration rates, suggesting that the two cell types arise and migrate independently.

Proliferation of goblet cells and vacuolated cells in the rabbit distal colon

Previous studies of colonic epithelial cell kinetics in mice and rats revealed a pattern similar to small intestine, where basally located stem cells proliferate, differentiating as they migrate towards the surface epithelium. Vacuolated and goblet cells are assumed to co-migrate at the same rate. The present study indicates that rabbit distal colon has more complicated epithelial cell kinetics. The zone of proliferation was detected immunohistochemically using proliferating cell nuclear antigen (PCNA) and confirmed with the use of colchicine to arrest dividing cells in metaphase. Migrating cells were tracked from the zero-hour position (PCNA labeling, mitosis) to positions 24, 48, 72 hrs by monitoring cell migration with the thymidine analog 5-Bromo-2-Deoxyuridine (BrdU). PCNA revealed a major proliferative zone in the upper third of the crypt column and the presence of mitotic figures after colchicine corroborated these results. Differentiated vacuolated cell proliferation was detected at three crypt sites: base, middle, and top of the crypt, while columnar cells arose from a population of dividing cells at the top of the crypt. Turnover of columnar and vacuolated cells occurred within 72 hrs. Goblet cells exhibited maximal proliferation at the crypt base and migrated at a much slower rate than the other cell types. In rabbit distal colon, populations of proliferating cells exist at multiple levels of the crypt column. Vacuolated and goblet cells differ in their labeling indices and migration rates, suggesting that the two cell types arise and migrate independently. Anat. Rec. 252:41–48, 1998. © 1998 Wiley-Liss, Inc.

Colonic Cell Proliferation in Normal Mucosa of Patients with Colon Cancer

Cell kinetics parameters have been analysed in colonic mucosa at different distances from a tumour in patients with colon carcinoma. Total cell number (TCN), H thymidine labelling index (TLI), mitotic index (MI), Goblet cell index (GCI) and the distribution of labelled cells along the crypt column (cell position frequency plot) were determined in well-aligned crypts. Total cell number, GCI and the labelled cell position frequency plots were similar in different samples from the same individual. A negative linear correlation between TCN and TLI was observed. The analysis of the cell position plots showed two patterns 1) with a high concentration in the bottom fifth of the crypt and 2) with frequent labelled cells at high positions. Whereas a negative correlation between overall TLI and the percent contribution to the TLI of the lowermost fifth was seen, the correlation was positive for the next 3 fifths and labelling was absent in the last part of the crypt.

Predictive value of proliferation, differentiation and apoptosis as intermediate markers for colon tumorigenesis.

In order to determine the prognostic significance of proliferation, differentiation, and apoptosis as intermediate markers for colon tumor development, these indices were measured during the promotion phase of tumorigenesis. Two hundred and sixty male Sprague-Dawley rats were provided with one of two fats (corn oil and fish oil) and two fibers (pectin and cellulose) plus or minus the carcinogen azoxymethane (AOM) and killed at two time points (18 and 36 wk) in a 2x2x2x2 factorial design. In vivo cell proliferation was measured immunohistochemically using incorporation of bromodeoxyuridine into DNA. Differentiation was assessed by binding of Dolichos biflorus agglutinin (DBA) to colonocytes. Apoptosis was measured by immunoperoxidase detection of digoxigenin-labeled genomic DNA. Adenocarcinoma incidence results at week 36 were 70.3% for corn oil + AOM and 56.1% for fish oil + AOM treatment (P < 0.05); no main effect of fiber was observed. At week 18, AOM treatment increased the number of cells per crypt column in the proximal colon compared with saline controls (P = 0.0358) and increased the proliferative zone in the distal colon compared with controls (P = 0.0073). However, changes in cell proliferation at week 18 did not predict the beneficial effect of fish oil versus corn oil. In contrast, DBA binding (the marker for differentiation) was higher in fish oil versus corn oil fed animals in both the proximal and distal colon and in each portion of the crypt (P = 0.0001). There were a greater number of apoptotic cells/crypt column in the proximal colon (P = 0.0019) and distal colon (P = 0.0358) with fish oil compared with corn oil, and indices of apoptosis also predicted certain fat/fiber interactions. Measurements of differentiation and apoptosis had greater prognostic value to detect dietary effects on tumor incidence than did measurements of cell proliferation.

Dietary modulation of colonic mucosal urokinase activity in rats.

The amount and type of dietary fibre ingested influences colonic luminal characteristics, especially the concentration of carbohydrate fermentation products such as butyrate. This study aimed to assess whether diets supplemented with fibres of differing fermentability (delivering different amounts of butyrate to the colon) influence mucosal activities of urokinase and brush border hydrolases, and epithelial turnover. Groups of five rats were fed one of four diets containing low (2%), highly fermented (guar 10% or oat bran 10%) or slowly fermented fibre (wheat bran 10%) for 4 weeks. Activities of urokinase, alkaline phosphatase, dipeptidyl peptidase IV and maltase were measured in mucosal homogenates of proximal and distal colon and from rectum. Proliferative kinetics were assessed in distal and proximal colon by the metaphase arrest technique. Hydrolase activities were similar across all four dietary groups but a significant difference was found for urokinase (P = 0.014). This was due to a reduction in urokinase activities of > 30% at the three sites in the wheat bran group compared with the other groups. Of proliferative indices, only crypt column height differed across the groups (P = 0.038) and was highest in rats fed wheat bran and lowest in those fed the low fibre diet (P = 0.047). The proportion of mitoses in the top one-fifth of the crypt also differed across groups (P = 0.038) due to the high values in the distal colon of the low fibre group. Thus, addition of a slowly fermented (but not highly fermented) fibre to the diet of rats reduces net urokinase activity in large bowel mucosa and increases the life span of colonic epithelial cells without changing activities of brush border hydrolases.

Aspirin, age, and proximity to lymphoid nodules influence cell proliferation parameters in rat colonic crypts

Recent epidemiological studies have demonstrated a correlation between regular aspirin (acetylsalicylic acid) use and decrease risk for the development of fatal colorectal cancer. An increase in the size of the cell proliferation compartment in colorectal crypts has been correlated with an increased risk for the development of colon cancer in animals and in humans. To determine if acetylsalicylic acid acts to decrease the size of the cell proliferation compartment, young (3 month) and old (22 month) rats were treated intragastrically with: 1 the vehicle for acetylsalicylic acid delivery (0.25% wt/vol carboxymetylcellulose in 0.15 N (HCl), 2 a single dose of acetylsalicylic acid (100 mg/kg), or 3 acetylsalicylic acid (30 mg/kg) given daily for 30 days. One day after the last treatment, colons were resected, fixed, sectioned and mounted on slides for immunohistochemical staining with a monoclonal antibody to proliferating cell nuclear antigen to assess cell proliferation parameters in the colonic crypts. The results were subjected to three way analysis of variance to assess the effects of: 1 rat age, 2 acute or chronic acetylsalicylic acid treatment, and 3 location of crypts over and away from aggregates of lymphoid nodules on the crypt proliferative parameters. Results demonstrated that: 1 acetylsalicylic acid treatment caused on overall decrease in the proliferative zone height, as measured in number of cells in the crypt column, 2 that crypts located over aggregates of lymphoid nodules had significantly higher proliferative activity than crypts located away from aggregates of lymphoid nodules, and 3 after chronic acetylsalicylic acid treatment there was a greater suppression of proliferative zone height in the crypts of old rats than in the crypts of young rats. In conclusion, acute and chronic intragastric delivery of acetylsalicylic acid caused an overall downward shift in the cell proliferation compartment of colonic crypts of young and of old rats. Whether or not acetylsalicylic acid administration will cause the same proliferative zone height response in carcinogen-treated rats is not yet established.

Analysis of crypt cell proliferation in coeliac disease using MI-B1 antibody shows an increase in growth fraction.

This study aimed to investigate the pattern of cellular proliferation and to calculate the growth fraction of small intestinal crypts in 24 patients--eight with untreated coeliac disease (CD), six with treated CD, and 10 controls with normal villous architecture. Duodenal biopsy specimens were stained with MI-B1 antibody using an immunoperoxidase method. Positive stained crypt cells were counted and their position within each intact crypt column was noted. These were used to construct proliferation index distribution curves for each cell position from which the crypt growth fraction for each group of patients was calculated. The crypt growth fraction was found to be higher in the untreated CD group (0.57) than in the treated patients (0.39) and the controls (0.44). The mean (SEM) proliferative index for each crypt was significantly higher in the untreated group (42.3 (10.8)%; p < 0.05) than in the treated CD (21.7 (8.5)%) and control (19.7 (7.5)%) groups and correlated closely with the surface:volume index and enterocyte cell height measurements in all three groups. An increased growth fraction may contribute to other changes in crypt cell kinetics to produce the histological changes seen in untreated CD.

Dietary modulation of rat colonic cAMP-dependent protein kinase activity

Malignant transformation of cells is associated with enhanced proliferation and alterations in cAMP-dependent protein kinase (PKA) activity. To investigate the role of PKA in normal colonic cell proliferation, PKA was characterized in rat colonic mucosa. In addition, rats were fed diets containing different fats (corn oil, fish oil) and fibers (pectin, cellulose, fiber free) to elicit varying levels of colonic cell proliferation in order to study this signaling system under normal physiologic conditions. Overall, PKA activities were higher in cytosolic compared to membrane fractions. PKA type II (PKA II) isozyme contributed 89 ± 1% and 96 ± 1% of total PKA activity in cytosolic and membrane fractions, respectively. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed the presence of mRNA for both the α and β isoforms of the regulatory subunits of PKA II. PKA activities were 21–33% higher in distal membrane and total distal fractions in rats fed a cellulose/corn oil diet compared to animals consuming the other fiber/fat diets. These effects were seen only in the distal colon, where the number of cells per crypt column was elevated only in animals fed the cellulose/corn oil diet relative to other diets. Diet-induced mitogenic responses did not involve significant changes in the relative activity of PKA I and II isozymes. These data demonstrate that dietary effects on PKA activity in the distal colon may be related to changes in cell differentiation as indicated by the number of cells per crypt column.

Immunohistochemical analysis of epithelial cell proliferation in normal-appearing rectal mucosa of patients with colorectal adenoma and cancer using an in vitro labeling method with bromodeoxyuridine.

To identify diffuse mucosal changes which may precede the development of colorectal cancer and a possible indicator for detecting high-risk populations, we immunohistochemically studied cell-cycle events in crypts of normal-appearing rectal mucosa of patients with colorectal adenoma and cancer using an in vitro labeling method with bromodeoxyuridine (BrdU). Biopsy specimens of endoscopically normal-appearing rectal mucosa were obtained during colonoscopy from 20 patients with colorectal adenocarcinoma, 20 with adenoma, and 15 without apparent colorectal diseases. The specimens were incubated with BrdU in vitro, and labeled S-phase cells were identified immunohistochemically using a monoclonal antibody to BrdU. Modification of the BrdU-labeling pattern in the normal appearing rectal mucosa, such as the presence of BrdU-labeled cells at the mucosal surface or in the upper one-fifth of the crypt column, was observed in 15 of the 20 patients with adenocarcinoma, 17 of the 20 patients with adenoma and 6 of the 15 controls. This upward shift in the frequency of proliferating cells in the crypt was significantly higher in the patients with colorectal adenoma and cancer than in the controls, and may be used to identify subjects at high risk for colorectal cancer.

Dietary fat quantity and composition alter colon cell kinetics in growing rats.

The effects of corn oil and beef tallow on the proliferation of colon mucosal cells in rats were investigated. In protocol 1, rats were fed diets containing 12 or 38% kJ from fat supplied by either corn oil or beef tallow. Colon crypt column cell number was examined histologically. The source of dietary fat had no effect on the number of cells per crypt column, but rats fed 38% fat had significantly fewer cells per crypt column in the proximal colon than rats fed 12%. Protocol 2 examined the effects of diets containing corn oil or beef tallow at 12, 30, or 37% kJ on the percentage of colon cells in phases of the cell cycle using flow cytometry and expression of proliferating cell nuclear antigen (PCNA). Rats fed corn oil had more cells in S phase compared to rats fed beef tallow. Rats fed 30 or 37% fat had more cells in G1 and fewer cells in G2 + M compared to rats fed 12%. Animals consuming the 12% corn oil diet or the 37% beef tallow diet had the fewest colon cells expressing PCNA, while those animals consuming the 37% corn oil diet or the 12% beef tallow diet had the greatest number of cells expressing PCNA. Based on combined interpretation of PCNA and cell cycle phases, the results suggest that diets high in saturated fat result in reduced colon cell proliferation whereas diets high in unsaturated fat do not.

Dietary fibers stimulate colonic cell proliferation by different mechanisms at different sites

The effect of dietary fiber type (cellulose, pectin, or oat bran) on colonic short-chain fatty acids (SCFA), luminal pH, and epithelial cell proliferation was examined in 60 male Sprague-Dawley rats. In vivo cell proliferation was measured by [3H]thymidine incorporation into DNA, pH was measured in vivo, and luminal SCFA were determined by gas chromatography. The pectin and oat bran diets produced higher concentrations of all types of SCFA and total SCFA than cellulose at every site. The higher the SCFA concentration, the lower was the pH at each site. In the cecum, the concentration of SCFA was positively associated with the number of cells per crypt column (r = 0.961), total cells per crypt (r = 0.963), and the proliferative zone (r = 0.845). In contrast, in the distal colon, there was no significant correlation between SCFA concentration and measurements of cell proliferation. These data suggest that fiber stimulates cecal cell proliferation through the production of SCFA. The effects of fiber on distal colonic cytokinetics are likely mediated through a different mechanism.

Colonic mucosal proliferation after pancreaticobiliary diversion in the hamster

The effect of pancreaticobiliary diversion (PBD) on the colonic mucosa was studied in hamsters over 5, 10, and 24 days. Sham-operated animals served as controls. At all three time intervals, experimental animals had increased plasma cholecystokinin concentrations and decreased gastrin concentrations. Five days after PBD, there was an increase in scintigraphically measured [3H]thymidine incorporation into colonic tissue. Correspondingly, there was an increase in the [3H]thymidine DNA labeling index of goblet cells in the colonic mucosa. The total number of cells in the colonic crypt columns were significantly increased on days 5, 10 and 24. Whether this proliferative response in the colon is due to increased release of cholecystokinin, enteroglucagon, other aberrations of hormones or growth factors, or simply an increased bile load on the colonic mucosa remains to be clarified. Such further studies may reveal an alternative animal model for studies on risk factors in colonic carcinogenesis.