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PubMed1986

Experimental colorectal cancer: the relationship of diet and faecal bile acid concentration to tumour induction.

Epidemiological studies have consistently suggested an aetiological relationship between certain dietary constituents, faecal bile acid (FBA) concentration and colorectal cancer. This study was designed to examine the effect of the dietary manipulation of fat and fibre on tumour induction and on various faecal characteristics in Albino Swiss rats. A total of 232 animals were maintained on one of four different diets for 4, 20 and 28 weeks respectively. The diets were classified as high fat high fibre, low fat high fibre, high fat low fibre and low fat low fibre. The groups were further sub-divided according to the administration of systemic azoxymethane (10 mg/kg per week) or saline over 12 consecutive weeks. The high fat low fibre diet was associated with the highest risk for tumour production and the low fat high fibre diet with the lowest risk. Statistically significant differences between all the diets were noted with the exception of a comparison between the high fat high fibre and low fat high fibre diets. The highest total concentration of free FBA was found in the faeces from animals fed low fibre containing diets. The results show a clear influence of both fat and fibre on tumour induction while, in this model, fibre was the principle determinant of faecal bile acid concentration.

Animals↗
PubMed1990

Effect of defunction on cytokinetics and cancer at colonic suture lines.

An intestinal suture line potentiates experimental carcinogenesis in its vicinity, probably due to adaptive hyperplasia. By contrast, a defunctioning colostomy causes distal hypoplasia, and fewer tumours develop. Male Sprague-Dawley rats (n = 160) were used to study adaptation (assessed by a stathmokinetic technique) and carcinogenesis (induced by azoxymethane) at an end-to-end anastomosis that was raised in either functioning or defunctioned left colon. Controls had no procedure and other rats had proximal colostomy alone. Defunction had a profound antitropic effect on the colon, reducing bowel length and weight and crypt cell production rate (CCPR) by 22-56 per cent. Anastomotic CCPR was increased by a factor of 2.6 over controls: mean(s.e.m.) values of 12.71(2.85) versus 4.87(0.41) cells/crypt/h (P less than 0.01), but defunction reduced this by 76 per cent to a mean(s.e.m.) value of 3.00(0.52) cells/crypt/h below that in the intact colon. In the left colon, 39-50 per cent of tumours were sited at the anastomosis. Compared with controls there were 77 per cent fewer tumours in defunctioned colon, but they still favoured the site of anastomosis. Neoplasms at the colostomy site accounted for 74-77 per cent of all right-sided tumours. Anastomosis and defunction have powerful but contrasting effects on colonic adaptation and carcinogenesis; when combined they tend to cancel each other out.

Adaptation, Physiological↗
PubMed1990

Experimental colonic carcinogenesis after gastric surgery.

Peptic ulcer surgery may predispose to the subsequent development of colorectal cancer. This experimental study has investigated the effects of gastric operations on colonic cell proliferation, bile acid excretion and carcinogenesis. Male Sprague-Dawley rats (n = 105) underwent sham operation, Pólya partial gastrectomy or vagotomy and pyloroplasty. The carcinogen azoxymethane was administered weekly for 6 weeks thereafter (total dose 60 mg kg-1). When the animals were killed 24 weeks after operation, colons were examined for mucosal mass, crypt cell production rate (CCPR) and tumour yield; faeces were assayed for contents of neutral steroids and bile acids (both total and individual). Morphometric indices and mucosal DNA content were similar in all three groups. Pólya gastrectomy reduced: (1) CCPR throughout the colon (by 42-65 per cent, P less than 0.002); (2) the number of rats with colorectal tumours (26 per cent versus 63 per cent, P less than 0.05); (3) faecal levels of neutral steroids and bile acids, notably hyodeoxycholic acid (P less than 0.01). Although vagotomy and pyloroplasty increased caecal CCPR, there were no consistent differences in faecal steroids and no alteration in tumour yield after the operation. These results fail to support clinical studies suggesting that gastric surgery predisposes to colonic carcinogenesis. Indeed, Pólya partial gastrectomy exerts a protective effect, probably by inhibiting colonic cell proliferation.

Adaptation, Physiological↗
PubMed2005

Abdominal obesity, insulin resistance, and colon carcinogenesis are increased in mutant mice lacking gastrin gene expression.

BACKGROUND: The authors recently reported that gastrin gene knockout (GAS-KO) mice had an increased risk for colon carcinogenesis in response to azoxymethane (AOM) compared with their wild type (WT) littermates. In the current report, the authors discuss the predisposition of GAS-KO mice to develop obesity and metabolic hormonal changes that may contribute to their increased risk of colon carcinogenesis. METHODS: The weight and deposition of fat was monitored in the mice over a 14 month period, using magnetic resonance imaging and nuclear magnetic resonance techniques. Changes in plasma concentrations of ghrelin, leptin, insulin, and glucose were assessed using radioimmunoassay analysis and enzyme-linked immunosorbent assays. Preneoplastic markers of colon carcinogenesis (aberrant crypt foci [ACFs]), in response to AOM, were measured in a subset of obese versus lean GAS-KO mice and were compared with the markers in WT mice. RESULTS: Increases in visceral adiposity were evident by age 2 months in GAS-KO mice, resulting in macroscopic obesity by age 7 months. Hyperinsulinemia and insulin:glucose ratios were increased significantly in GAS-KO mice as young as 1 month and preceded alterations in nonfasting leptin and ghrelin levels. The number of ACFs per mouse colon were increased significantly in the following order: obese GAS-KO mice > lean GAS-KO mice > WT mice. Fasting plasma insulin levels were 0.88 +/- 0.1 ng/mL, 1.45 +/- 0.3, and 2.76 +/- 0.9 ng/mL in the WT, GAS-KO lean, and GAS-KO obese mice, respectively. CONCLUSIONS: The current results suggest the novel possibility that loss of amidated gastrins may increase adipogenesis, hyperinsulinemia, and colon carcinogenesis in GAS-KO mice. The increase in colon carcinogenesis may be due in part to hyperinsulinemia, increased obesity, and other associated hormone changes that were measured in GAS-KO mice.

Animals↗
PubMed2002

Steady state levels of transforming growth factor-beta1 and -beta2 mRNA and protein expression are elevated in colonic tumors in vivo irrespective of dietary lipids intervention.

Colonic tumors of human origin produce abundant transforming growth factor (TGF)-beta suggesting that TGF-beta is critical to their growth. Dietary lipids regulate a number of growth factors including TGF-beta. Whether elevated TGF-beta levels are consistently expressed in colonic tumors irrespective of the environmental milieu in an in vivo model is not known and forms the main objective of the present study. Male F344 rats were injected with azoxymethane, 10 weeks later, rats bearing preneoplastic lesions were fed a low fat (5% corn oil) diet and 3 high fat (5% corn oil with 18% corn oil, fish oil or beef tallow) diets for 16 weeks. Colonic tumors and mucosae were processed and assessed for TGF-beta status. TGF-beta1 and -beta2 mRNA levels were upregulated in colonic tumors more than in mucosae of all diet groups. Dietary lipids modulated TGF-beta mRNA in both tumors and mucosae, high corn and fish oil diets upregulated TGF-beta1 significantly more than the low fat corn oil or high fat beef tallow diets. Immunohistochemical assessments of tissues with different biological features revealed that TGF-beta1 and -beta2 were elevated in tumors and in selected microscopic preneoplastic lesions compared to normal mucosae. This is the first in vivo study, documenting that developing colonic tumors acquire upregulated TGF-beta phenotype even in the presence of lipid environments capable of differentially regulating TGF-beta in normal mucosae. Elevated expression of TGF-beta in a selected subset of microscopic preneoplastic lesions suggests that TGF-beta plays an important role on both early and late stages of colon carcinogenesis.

Animals↗
PubMed2005

Low doses of beta-carotene and lutein inhibit AOM-induced rat colonic ACF formation but high doses augment ACF incidence.

Epidemiological studies suggest that carotenoids such as beta-carotene and lutein play an important role in reducing the risk for several cancers. However, in colon cancer there is ambiguity with regard to the role of these compounds in that both preventive effects and tumor promotion have been observed. In the present study we observed that male F344 rats were able to tolerate up to 2,500 ppm of beta-carotene as well as of lutein. We have then assessed the chemopreventive efficacy of beta-carotene and lutein at dose levels of approximately 4 and 8% of the 2,500 ppm tolerated dose (TD) and also approximately 40 and 80% of the TD on azoxymethane (AOM)-induced colon carcinogenesis, using aberrant crypt foci (ACF) as a surrogate biomarker for colon cancer. Throughout the experiments, 5-week-old male F344 rats were fed the control diet (modified AIN-76A) or experimental diets containing 100 or 200 ppm (approximately 4 or 8% of the 2,500 ppm TD), or 1,000 or 2,000 ppm ( approximately 40 or 80% of the 2,500 ppm TD) of beta-carotene and lutein (n=10 rats/group). After 2 weeks on the experimental or control diets, all animals were injected with AOM (15 mg/kg body wt., once weekly for 2 weeks). At 14 weeks of age, all rats were killed, and their colons were evaluated for ACF. Administration of 100 or 200 ppm of beta-carotene inhibited AOM-induced total colonic ACF formation by 24% (p<0.01) and 36% (p<0.001), respectively, whereas lutein at 200 ppm produced a 27% inhibition (p<0.01) yet had no significant effect at the 100 ppm dose level. Surprisingly, administration of 1,000 or 2,000 ppm of beta-carotene and lutein increased colonic ACF formation in a dose-dependent manner, i.e., to 124% and 144% for the former and 110% and 159% for the latter. These results clearly suggest that further studies are warranted to determine whether the increase in ACF incidence by high doses of beta-carotene and lutein will also lead to an increase in tumor outcome. Taken together these data indicate that the chemopreventive activity of beta-carotene and lutein against colon carcinogenesis depends on the dose level.

Animals↗
PubMed2007

Diet supplemented with citrus unshiu segment membrane suppresses chemically induced colonic preneoplastic lesions and fatty liver in male db/db mice.

The modulatory effects of dietary citrus unshiu segment membrane (CUSM) on the occurrence of aberrant crypt foci (ACF) and beta-catenin accumulated crypts (BCACs) were determined in male C57BL/KsJ-db/db (db/db) mice initiated with azoxymethane (AOM). Male db/db, db/+ and +/+ mice were given 5 weekly subcutaneous injections of AOM (15 mg/kg body weight), and then they were fed the diet containing 0.02%, 0.1% or 0.5% CUSM for 7 weeks. At Week 12, a significant increase in the numbers of ACF and BCAC was noted in the db/db mice in comparison with the db/+ and +/+ mice. Feeding with CUSM caused reduction in the frequency of ACF in all genotypes of mice and the potency was high in order of the db/db mice, db/+ mice and +/+ mice. The number of BCACs was also reduced by feeding with CUSM, thus resulting in a 28-61% reduction in the db/db mice, possibly due to suppression of cell proliferation activity in the lesions by feeding with CUSM-containing diet. Clinical chemistry revealed a low serum level of triglyceride in mice fed CUSM. In addition, CUSM feeding inhibited fatty metamorphosis and fibrosis in the liver of db/db mice. Our findings show that CUSM in the diet has a chemopreventive ability against the early phase of AOM-induced colon carcinogenesis in the db/db as well as db/+ and +/+ mice, indicating potential use of CUSM in cancer chemoprevention in obese people.

Animals↗
PubMed1994

Aberrant crypt foci and colon tumors in F344 rats have similar increases in proliferative activity.

Increased proliferative activity has been described frequently in the colons of animals treated with colon carcinogens and of patients at increased risk of colon cancer; it has been proposed as an intermediate biomarker of colon cancer. Aberrant crypt foci, microscopic lesions identified in whole-mount preparations of colons, are thought to be putative pre-neoplastic lesions. The present studies were carried out to evaluate the proliferative activity of aberrant crypt foci at several different time periods, and of tumors after a single dose of azoxymethane (AOM) in F344 rats. Rats were injected with 5-bromo-2'-deoxyuridine (BUdR) 1 hr before killing. Aberrant crypt foci and tumors were identified and marked in the whole-mount specimens, embedded in glycol methacrylate, and evaluated for histochemically demonstrable hexosaminidase activity. Hexosaminidase is known to be altered in over 95% of aberrant crypt foci. Serial sections were evaluated for BUdR incorporation immunohistochemically with a monoclonal antibody. The mean proliferative activity of aberrant crypt foci in the distal colons was found to be increased 3- to 4-fold over that of the adjacent normal crypts at every time period analyzed (4 to 36 weeks) and was comparable to that seen in benign and malignant colon tumors in the same animals. The observed increase in proliferative activity further supports the hypothesis that aberrant crypt foci are putative pre-neoplastic lesions. Similar aberrant crypt foci, identified in human colons at increased risk of colon cancer, may provide important biomarkers for this common human cancer.

Adenocarcinoma↗
PubMed1994

Initiated stem cells in murine intestinal carcinogenesis: prolonged survival, control by NK cells, and progression.

Weekly injections of dimethylhydrazine (DMH) (25 mg/kg), or azoxymethane (AOM) (8 mg/kg) to young adult male CDI mice for 1-2 months produced generalized intestinal crypt hyperplasia, which we measured in duodenum in terms of number of interphase and mitotic cells present in crypts. As shown earlier, the crypts expanded because of the presence of a hyperproliferative "initiated" crypt subpopulation which was also sensitive to natural killer (NK) cells. Hyperplasia was thus present as long as NK activity was suppressed by the carcinogen treatment. After interruption of the treatment for periods of 1, 2, 3, 6 and 10 months in the various groups, hyperplasia soon regressed as a result of elimination of the subpopulation by the recovering NK cells. When NK activity was once again eliminated during the terminal days of these "interruption periods" (by injections of anti-asialo GM-I antibody, alpha AGM-I), the original hyperplasia was fully reconstituted, apparently from stem cells of the subpopulation which survived up to 10 months in their crypt base location. These "initiated stem cells" represented, then, the original carcinogenic insult during the pre-cancerous period. They also appeared to be the source of the eventual neoplasia, as treating the animals with mutagens during the interruption periods produced specific changes in crypt base histology: new "crypt base basophilic" (CBB) cells appeared which produced large accumulations as well as microscopic tumors when NK activity was suppressed (by alpha AGM-I). Some of the initiated stem cells were apparently transformed into neoplastic ones which remained under NK control, the NK cells preventing the establishment of their progeny. Further experiments indicated that, although the initiated stem cells are not eliminated by normal NK activity, activated NK cells can kill them, thereby eliminating the potential source of neoplasia.

1,2-Dimethylhydrazine↗
PubMed1995

Inhibition of aberrant crypt growth by non-steroidal anti-inflammatory agents and differentiation agents in the rat colon.

Aberrant crypts are aggregates of single to multiple colonic crypts evidencing hallmarks of dysplasia and may be the earliest detectable pathological lesions for colon cancer. The aberrant crypt assay has been developed in 2 protocols. In one, putative chemoprevention agents are tested for inhibitory effects when administered concomitantly with a carcinogen. In the other, the objective of this study, aberrant crypts were induced in F344 rats by parenteral injection of the colon carcinogen azoxymethane (AOM) and allowed to develop for 4 weeks, when an average of 90-100 aberrant crypt foci per colon were found in the methylene blue-stained colon. Then, during the second 4 weeks of the experiment, aberrant crypts were allowed to further develop to a frequency of > 150 foci per colon, a time when multi-crypt foci were observed. During this time we tested the inhibitory effects of 4 analgesic drugs and 2 differentiation agents for effects of aberrant crypt growth and development. We found the non-steroidal anti-inflammatory drugs piroxicam, aspirin and ibuprofen, but not acetaminophen, to be effective in suppressing aberrant crypt formation or the progression to foci of multiple aberrant crypts. Treatment with chemosuppressing agents 13-cis-retinoic acid (13-cRA) and 4-hydroxyphenretinamide (4-HPR), known differentiating agents, however, did suppress expansion of aberrant crypt foci, with 13-cRA being the much more potent agent.

Acetaminophen↗
PubMed2007

Deoxycholic acid promotes the growth of colonic aberrant crypt foci.

AKR/J mice are resistant to the tumorigenic properties of the colon carcinogen, azoxymethane (AOM). Following AOM exposure, limited numbers of preneoplastic lesions, referred to as aberrant crypt foci (ACF), are formed in the colon, and their progression to tumors rarely occurs. To determine whether genetic resistance can be overcome by exposure to a dietary tumor promoter, AOM-exposed AKR/J mice were fed a diet containing 0.25% deoxycholic acid (DCA). DCA exposure was begun 1 wk prior to or 1 wk after tumor initiation with AOM. Mice placed on the DCA diet prior to AOM treatment developed a significantly higher multiplicity of ACF compared to AOM-exposed mice fed a control diet (15.50 +/- 0.96 vs. 6.17 +/- 0.48, respectively; P < 0.05). When DCA exposure was begun after AOM treatment (post-initiation), ACF formation was further enhanced (34.00 +/- 1.22). Interestingly, increased numbers of ACF were associated with the presence of nuclear beta-catenin, assessed by immunohistochemistry. While approximately 33% of ACF from mice exposed to DCA prior to AOM treatment contained positive nuclear beta-catenin staining, approximately 77% of ACF from mice fed DCA after AOM were positive. Accumulation of nuclear beta-catenin was not associated with a loss of E-cadherin from the plasma membrane, although loss of APC staining was a consistent feature of most AOM-induced ACF, regardless of DCA exposure. These results demonstrate that exposure to DCA, an important digestive component, is sufficient to sensitize the resistant AKR/J colon to formation of high-grade dysplasia, and that nuclear translocation of beta-catenin may play an important role in this process.

Animals↗
PubMed2005

Dietary supplement of isohumulones inhibits the formation of aberrant crypt foci with a concomitant decrease in prostaglandin E2 level in rat colon.

Male Fischer 344 rats were subcutaneously injected with azoxymethane (AOM) twice weekly at a dose of 15 mg/kg and were fed with freeze-dried (FD) samples of beer brewed without hops (non-hops beer), beer with hops at 4 times the amount of regular lager beer (x 4-hops beer), and isomerized hop extract (IHE) for the whole experimental period (I/PI) or for the post-initiation period (PI) only. Feeding FD beer samples at a dose of 1% significantly decreased the number of aberrant cryp foci (ACF) in the PI protocol over five weeks.x4-hops beer showed stronger inhibitory effects on the development of the numbers of aberrant crypts per focus and large ACF with four or more crypts than non-hops beer. Feeding IHE to rats at a dose of 0.01% or 0.05% in either the I/PI or PI experiment significantly reduced the numbers of ACF. Prostaglandin E2 (PGE2) levels in colonic mucosa of AOM-treated rats were significantly reduced by feeding of IHE. PGE2 production induced by lipopolysaccharide/interferon-gamma (LPS/IFN-gamma) in RAW264.7 cells was also reduced by treatment with IHE and isohumulone in a dose-dependent manner. These observations suggest that isohumulones show chemopreventive effects on ACF formation in rat colon by inhibiting the production of PGE2.

Animals↗
PubMed1995

1H MR visible lipids in colon tissue from normal and carcinogen-treated rats.

Metabolic characteristics of colon mucosa, submucosa, muscularis and tumour specimens from four control (n = 105) and nine carcinogen (azoxymethane)-treated (n = 91) Sprague-Dawley rats were investigated by ex vivo 1H MRS. Ninety-seven per cent of pure mucosa samples (n = 59) yielded spectra with narrow lipid resonances (chemical shift delta of -(CH2)n-, 1.3 ppm; linewidth at half-height v1/2, 30-50 Hz). Eighty-two per cent of control mucosa samples with histologically proven submucosa contamination (n = 11) and 46% of control cross-sections (containing mucosa, submucosa and muscularis; n = 57) yielded spectra with broad lipid resonances (delta-(CH2)n-, 1.5 ppm; v1/2, 80-100 Hz) identical to those of adipose tissue surrounding rat colon. Thirty per cent of tumour samples (n = 10) yielded spectra with narrow lipid resonances while 70% contained no significant amount of MR visible lipids. We conclude that (i) lipids giving rise to broad resonances are in the heterogeneously distributed adipocytes of submucosa, (ii) lipids giving rise to narrow resonances are within the mucosa in an unknown structural environment, and (iii) the type and distribution of lipids in human and rat colon are similar. Tumours contained significantly more taurine than pure control mucosa (n = 15; p < 0.004) and pure mucosa containing aberrant crypt foci (putative preneoplasm, n = 36; p < 0.002). Our results suggest that the rat colon is a good model for 1H MR investigations of human colon carcinogenesis.

Animals↗
PubMed2000

Nitric oxide synthase inhibition promotes carcinogen-induced preneoplastic changes in the colon of rats.

l-Arginine is metabolized either to polyamines through arginase and ornithine decarboxylase (ODC) activities or to citrulline and nitric oxide (NO, nitrogen monoxide) through the NO synthase (NOS) pathway. Polyamine levels and ODC activity are high in tumor cells. The aim of this study was to test whether N(G)-nitro-l-arginine methyl ester (l-NAME), an inhibitor of NOS, modulates colon carcinogenesis. Adult male Wistar rats were treated with azoxymethane (AOM, 15 mg/kg ip), a chemical carcinogen, once a week for 2 weeks. One week after the second injection the rats were randomly divided into two groups. One group (n = 8) received l-NAME (10 mg/kg body wt/day) in drinking water. The control group (n = 8) received tap water. After 5 weeks, the rats receiving l-NAME showed enhanced mean basal arterial blood pressure, decreased heart rate, and a significant decrease of the cGMP content in the colonic mucosa. In both groups, AOM induced the formation of colonic aberrant crypt foci (ACF). In l-NAME-treated rats, the number of ACF was higher than in controls by 47%. ODC activity was enhanced by 11-fold. S-Adenosyl-methionine-decarboxylase activity and putrescine concentration were significantly increased in the colonic mucosa of l-NAME-treated rats. The data suggest that l-NAME promotes carcinogen-induced preneoplastic changes in the colon by inhibiting NOS activity and by stimulating polyamine biosynthesis.

Adenosylmethionine Decarboxylase↗
PubMed1986

Androgen receptors in experimentally induced colon carcinogenesis.

Sex hormones may play a role in colonic carcinogenesis, as evidenced by epidemiologic and experimental data showing different tumor rates in males and females. We investigated the effects of hormonal manipulation on tumor development and on androgen receptor binding in both colonic wall and experimentally induced tumors in male rats. Five of six groups, each with 40 animals, were given 10 weekly s.c. injections of azoxymethane (AOM), 7.5 mg/kg body weight. Group-I served as normal controls. Group-II received AOM only. Group-III was castrated 2 weeks prior to carcinogen treatment. Group-IV was castrated similarly and then hormone substituted with testosterone propionate. Group-V was chemically castrated with the anti androgen cyproterone acetate. Group-VI was castrated and given hormone vehicle. Scatchard analysis for androgen receptors in cytosol from normal colonic wall and tumor was performed with 3H-methyltrienolone as the ligand. Androgens were found to have an inhibitory effect on carcinogenesis: chemical castration increased colonic tumor development (P less than 0.05 for multiplicity), and testosterone administration produced a borderline statistically significant reduction in tumor incidence in surgically castrated rats (P less than 0.053), particularly in the right colon. Specific binding sites for androgen with high affinity and low capacity were found in the colonic wall of all groups. Receptor density was not altered by AOM administration, but increased after surgical castration. Receptor density was markedly lower in tumors than in normal colonic wall. Receptor binding sites in tumors were not altered by the various hormonal manipulations. Our study demonstrated that although cytoplasmic androgen receptors are present in colonic wall and in experimental tumors, AOM-induced colonic carcinogenesis appears to be only mildly affected by manipulation of androgens.

Animals↗
PubMed1990

Methane excretion and experimental colonic carcinogenesis.

To examine the association between methane (CH4) excretion and experimental colonic carcinogenesis, we measured CH4 excretion in rats treated with the colonic carcinogen azoxymethane (AOM, 7 mg/kg weekly for 10 weeks) and paired controls. CH4 excretion was not initially detected in either experimental or control groups, but all animals acquired positive CH4 excretion status by time of sacrifice (week 26). There was no difference between groups or among AOM-treated animals with and without tumors in the median time to onset of detectable CH4 excretion or in the amount of CH4 excreted. Our results fail to provide support for a link between CH4 excretion and experimental colonic dysplasia or adenocarcinoma.

Adenocarcinoma↗
PubMed1987

Dietary manipulation during experimental colorectal carcinogenesis: a morphological study in the rat.

The effect of the dietary manipulation of fat and fibre on the gross pathological, histopathological and scanning electron microscopic appearances of colonic mucosa was studied before and during experimental carcinogenesis in 232 male Albino Swiss rats. Carcinogen treated animals were given 12 consecutive weekly injections of Azoxymethane in a dose of 10 mg/kg per week. The animals were divided between four dietary groups (1: high fat high fibre, 2: low fat high fibre, 3: high fat low fibre and 4: low fat low fibre). The colorectal morphology was assessed at autopsy using standard histopathological techniques. In addition, scanning electron microscopic studies on selected samples were performed. A scoring system was introduced to allow a more accurate comparison of the surface architectural appearances. The high fat low fibre diet was associated with the greatest risk for macroscopic tumour production and the low fat high fibre diet with the lowest risk. Statistically significant differences between each of the dietary groups were noted with the exception of the comparison for tumour induction between the high fat high fibre and low fat high fibre dietary groups. Histopathological analysis confirmed the inter dietary relationships with respect to the extent of neoplastic change. The scanning electron microscopic study revealed that both dietary manipulation and carcinogen treatment influenced the surface characteristics. Control animals fed diet 2 (low fat high fibre) but not treated with carcinogen, showed the greatest deviation from the normal appearances. Animals treated with carcinogen and fed diet 3 (high fat low fibre) consistently showed the greatest surface abnormalities.

Animals↗
PubMed1989

An investigation of colon cancer associated with urinary diversion.

The mechanism by which ureterocolic anastomoses promote cancer of the colon is uncertain. To investigate the role of anastomotic healing, rats were exposed to the colon carcinogen azoxymethane after which they had either 1) a sham operation, 2) colotomy with suture, or 3) colovesical anastomosis, performed randomly. The first two groups had an equally low frequency of colon cancers, whereas rats with colovesical fistulas had a significantly higher frequency, and cancers were concentrated at the anastomotic site. It was concluded that prompt healing does not promote cancer in this model. It is probably not responsible for suture-line recurrences seen clinically, nor for the increased frequency of cancer at the site of urinary diversion into the colon.

Adenocarcinoma↗