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-Cellulose and Fish Oil Reduces Aberrant Crypt Foci Formation and Modulates Other Possible Markers for Colon Cancer Risk in Azoxymethane-Treated Rats1
*
CSIRO Health Sciences and Nutrition, Adelaide, South Australia;
Department of Physiology, University of Adelaide, South Australia; and
**
Department of Medical Nutrition, Stockholm University and Karolinska Institutet, Huddinge, Sweden
2To whom correspondence should be addressed. E-mail: graeme.mcintosh{at}hsn.csiro.au.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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-cellulose (Solkafloc) or resistant starch (RS; Hi-maize) at 10 g dietary fiber/100 g diet, combined with fish oil (FO) or sunflower seed oil (SSO) at 10 g/100 g diet, and lard added to all diets at 10 g/100 g, to provide a total of 20 g mixed fat/100 g diet. Sprague-Dawley rats (28 d of age) consumed diets for 4 wk and then two doses of AOM (15 mg/kg body) were administered 1 wk apart by subcutaneous injection. Rats were killed after 13 wk of consuming experimental diets. Colons were fixed in formalin and aberrant crypt foci (ACF) were quantified after staining. ACF counts were higher (+66%, P < 0.01) in rats fed SSO and RS, than in those fed -cellulose and FO. Rats fed FO had 19% fewer ACF than those fed SSO (P < 0.05). -Cellulose was associated with the highest cecal butyrate concentration (P < 0.001), the highest ß-glucuronidase specific activity (P < 0.001) and the lowest cecal water cytotoxicity (P < 0.001) relative to soy fiber– and RS-fed rats. There were inverse correlations between the number of ACF and cecal butyrate concentration (r = -0.33, P < 0.05) and between cecal water cytotoxicity and ß-glucuronidase activity (r = -0.70, P < 0.001). The greatest protection was associated with -cellulose as the fiber source and FO as the fat source as measured by colon ACF numbers in rats.
KEY WORDS: • fiber • polyunsaturated fatty acids • aberrant crypt foci • cecal water cytotoxicity • rats
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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), showed that the fiber-rich, low fat diet consumed by an African indigenous population was associated with a very low incidence of colon cancer compared with the high incidence associated with the high fat, low fiber diets consumed in Western countries. Other human case-control studies support Burkitt’s findings by showing that a large quantity of fiber in the diet is associated with a lower colon cancer incidence (2
). The preferred diet to reduce colon cancer risk is considered to be a low fat, high fiber diet (2
–5
). However, the sources, as well as the quantity of fat and fiber consumed must be considered when examining their effects on colon carcinogenesis.
Dietary fibers are polysaccharides that escape digestion in the small intestine. They are further classified by their intestinal solubility, plant source and degree of bacterial fermentation upon reaching the colon (6
,7
). Insoluble fibers, such as -cellulose from wheat bran, reduce intestinal transit time and increase fecal bulking, thereby reducing mucosal exposure to potential carcinogens or tumor promoters (8
,9
). Insoluble fibers, relative to soluble fibers, largely resist fermentation and have been shown to be more protective against colon cancer in animal models (10
,11
) and in humans, but the evidence is inconsistent (12
). A recently reported intervention study that examined the influence of wheat bran added to diets of people with previously removed colon polyps did not show any significant effects (13
). However, the study had a major problem with compliance in the elderly population, such that the conclusion may have reflected more the inadequacies of the study than the finding that wheat bran did not affect polyp recurrence. By contrast, the Australian polyp intervention study showed clear evidence of reduced polyps when wheat bran and lowered dietary fat intake influences were combined (14
).
It is unclear whether bacterial fermentation of soluble dietary fiber in the colon inhibits or promotes colon carcinogenesis. The colonic fermentation of resistant starch (RS),3
a product found in some cereal grains and cooked cold or raw potato, is thought to increase the concentration of short-chain-fatty acids (SCFA), in particular, butyrate (15
). Epidemiologic studies suggest that the reduced incidence of colon cancer associated with starch consumption may be due to the butyrate generated by starch-induced colonic fermentation (16
–18
). Butyrate has been shown to reduce aberrant crypt foci (ACF) formation (preneoplastic lesions used as a marker of early carcinogenesis) in rats (19
,20
), as well as to promote apoptosis (programmed cell death) and to control proliferation in human colon cancer cells in vitro (21
,22
). Animal studies have revealed that feeding a diet high in RS enhances the risk of colon cancer development (23
,24
). RS combined with wheat bran, however, has been associated with reduced risk (25
).
Another source of fiber, which has a questionable influence on colon carcinogenesis, is the fermentable cotyledonary soy fiber. Barnes et al. (26
) reported a diminished occurrence of tumors in rats fed soybean bran. The anticarcinogenic effect associated with soybeans has been linked to isoflavones, the phytochemicals present in soybeans (27
,28
). However, other studies have shown an increased risk of tumor development in the colon when rats consuming legumes such as soybeans or chickpeas as protein source were compared with those ingesting dairy proteins (29
–31
).
Some dietary fatty acids appear to be more protective against colon cancer than others. The long chain (n-3) polyunsaturated fatty acids (PUFA) (32
), such as eicosapentaenoic acid [20:5 (n-3)] and docosahexaenoic acid (DHA) [22:6 (n-3)], occurring in fish oil are considered protective. On the other hand, (n-6) PUFA such as linoleic acid [18:2 (n-6)], found in sunflower seed and corn oil, have been associated with promotion of colon cancer in rodent models (33
,34
). Reduction of colon tumor incidence and multiplicity in rats has been seen in those fed (n-3) PUFA (35
). These (n-3) PUFA may protect against colon carcinogenesis via several mechanisms, one of which may involve their ability to inhibit inflammation, otherwise stimulated by large quantities of (n-6) PUFA consumed in the diet (36
). Other mechanisms for the protectiveness of fish oil compared with corn oil include increased apoptosis and differentiation in rats with colon cancer (37
,38
).
This study investigated the influence of two fat and three fiber types on fermentation and azoxymethane (AOM)-induced formation of ACF. These components were provided to mimic a typical "Western" diet but with a high fiber intake. Fiber sources compared were the soluble soy cotyledonary fiber and RS, and the insoluble, inert -cellulose. The fiber sources were combined with one of two fat sources, i.e., fish oil (FO), rich in (n-3) PUFA, and sunflower seed oil (SSO), rich in (n-6) PUFA.
Along with ACF, other biomarkers associated with colon cancer risk were measured, including cecal water cytotoxicity (39
) and cecal SCFA concentration, including butyrate (24
). Cecal enzyme activity (40
,41
) and bacterial contents (42
) were also measured.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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Diets were based on the AIN-93G formula (43
), modified to contain fiber at 10 g/100 g and fat at 20 g/100 g to imitate a high fiber, high fat diet in humans. The three fiber sources used were: soy cotyledonary fiber as Fibrim (Protein Technologies International, New South Wales, Australia), -cellulose as Solkafloc (James River, Berlin, NH) and RS as Hi-maize (Starch Australasia, New South Wales, Australia). The two PUFA sources used were fish oil (Tuna fish oil Hi-DHA 23N3, Numega Lipids, Victoria, Australia) and sunflower seed oil (ETA, Victoria, Australia) combined 50:50 by weight with lard (George Chapman, South Australia). The three fiber sources were combined separately with the two fat types to provide six experimental diet treatments, whose compositions are shown in Table 1
. Diets were balanced for energy, calcium (0.2 g/100 g) and vitamin concentrations. The diets containing fish oil contained 
0.8 g/100 g linoleic acid. All ingredients were mixed, stored at 4°C and fed in powdered form, except for fish oil, which was added just before feeding to maintain freshness and palatability.
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Male Sprague-Dawley rats (n = 60; 3 wk of age) from the Animal Resource Center (Murdoch University, Perth, West Australia) were housed in wire-bottomed cages in a 23°C air-conditioned environment with a 12-h light:dark cycle. At 28 d of age, rats were assigned by weight to one of six dietary treatment groups (mean body weight 124 ± 0.5 g, n = 10). Rats had free access to experimental diets and water. The animal ethics committees of CSIRO, Health Science and Nutrition and the University of Adelaide, South Australia approved experiments involving animals before experimentation.
After 4 wk of consuming the experimental diets, AOM (Sigma Chemical, St Louis, MO) was injected subcutaneously in 2 doses (15 mg/kg body), 1 wk apart to induce ACF in the colons (31
,35
). Rats were placed in metabolic cages for 48 h each at wk 7 and 9 for the measurement of food and water intake and urine and feces outputs. Fresh feces were collected at wk 10 and 12 and stored at -20°C. Rats were killed by exsanguination after 13 wk of diet treatment after anesthesia with Fluothane and oxygen. Ceca and colons were removed. The colons were opened longitudinally and their contents weighed before being fixed flat between two pieces of filter paper in 100 mL/L buffered formalin for ACF analysis. Cecal contents were removed, weighed and aliquots stored at -20°C in sealed containers before biochemical analysis. For SCFA analysis, 3 mL Milli-Q water (Millipore Corp., Bedford, MA) was added to 0.5 g cecal contents and stored at -20°C. PBS (3 mL) was added to 0.5 g cecal contents and stored at -70°C for ß-glucuronidase enzyme analysis.
ACF assay.
Aberrant crypt foci (ACF) formation was assayed according to the method of Bird (19
) and counted using a standard light microscope (50X magnification). Colons were divided into proximal and distal sections by halving the colon between the herring bone region and the distal Peyer’s patch. ACF were distinguished from normal crypts by their thicker, darker-stained and raised walls, with elongated, slit-like lumens.
Biochemical analyses.
For SCFA concentration measurement, thawed cecal contents in deionized, distilled samples were homogenized and assayed after the addition of 50 µL of 10 mmol/L internal standard (-methyl valeric acid, Sigma Chemical). The samples were analyzed for SCFA (acetic, propionic and butyric acids) using a Shimadzu GC-17a gas chromatograph fitted with a BPX-21 megabore capillary column (25 m x 0.5 mm) (SGE, Victoria, Australia) based on a method previously published (11
).
To measure ß-glucuronidase, thawed samples (in PBS) were prepared according to the method of Goldin and Gorbach (45
) as modified by Jenab and Thompson (40
), but without the 0.3 mol trichloroacetic acid/L in the final step, before phenolphthalein color development and spectrophotometric assay. Analysis of samples was performed on a Varian Cary 1E UV-visible spectrophotometer (Varian Australia, Melbourne, Australia), at 540 nm absorbance using buffer as a blank. Specific ß-glucuronidase activity was expressed as µmol phenolphthalein released/(mg cecal protein · h). Cecal protein concentration was measured by the spectrophotometric method of Lowry (46
).
ATP concentration, as an indicator of cecal microbial content (42
), was measured by the method of Lundin and Thore (47
) using the firefly luciferase ATP bioluminescent assay kit (Sigma Chemical). Emission was read at 540 nm in a Hitachi fluorescence spectrophotometer.
Fecal fat concentration was used to indicate the risk of cancer (30
). Fecal samples collected from metabolic cages were weighed both before and after drying (14 h, 85°C) before fecal fat extraction, using chloroform/methanol according to the method of Folch (48
). The acid-soluble lipid was also removed and the fecal fat concentration expressed as a percentage of total fecal weight.
Cell culture analysis.
The cytotoxicity of cecal water was assayed using a modification of a method described (49
). Cecal contents were thawed and 0.5 g was diluted with 3 mL of water and centrifuged at 150,000 g for 50 min. The supernatant was collected and used in the cecal water cytotoxicity assay according to the method of Van Munster et al. (50
). Cells from the human colon cancer cell line (HT-29) were cultured in Dulbecco’s modified Eagle’s medium (Trace BioScience, Victoria, Australia) and plated in 5 x 96 well plates (15,000 cells/well). The Formazan dye, MTT [tetrazolium salt 3-(4,5-dimethylthiazol)-2,5-diphenyl tetrazolium bromide, Sigma Chemicals] was used to detect cell survival after incubation of cells for 1 h with 100 µL cecal water. Cell survival was read as absorbance at 570 nm using a SpectraMAX 250 ELISA Plate Reader (Molecular Devices, Sunnyvale, CA) and expressed as a percentage of maximal absorption of control cells incubated with PBS.
Statistical analysis.
Means ± SEM were calculated for each dietary treatment group (n = 10). The FO/soy group (n = 9) had one rat die of pneumonia. Pooled SEM and main effects of fat and fiber and their interactions were identified using two-way ANOVA with the SAS software package (Version 8.0, SAS Institute, Cary, NC). Differences between individual groups were determined using Tukey’s post-hoc test. Significance of difference was established at P < 0.05.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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There were fewer ACF in the whole colon of -cellulose–fed rats compared with RS-fed rats (P < 0.05) and soy fiber–fed rats (P < 0.05) (Table 2
). The total colon had 19% fewer ACF (P < 0.05) in rats consuming FO compared with those consuming SSO, independent of fiber source (Table 2)
. Rats fed FO exhibited a 24% reduction (P < 0.05) of ACF in the proximal colon and 15% reduction (P = 0.064) in the distal region compared with the same regions in the SSO-fed rats (P < 0.05). The highest number of ACF in the distal region was observed in SSO/RS-fed rats and the lowest was in the FO/-cell group (P < 0.01).
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4 aberrant crypts was suppressed in rats fed FO compared with those fed SSO (P < 0.05) (Table 2)
. Dietary fiber also affected the development of ACF with 4 aberrant crypts with pooled means generally greater in soy fiber–fed rats, compared with -cellulose– and RS-fed rats (P < 0.01). In the distal colon, there were no overall fat or fiber effects, nor any interactive effects (P > 0.05). However, FO/-cell–fed rats had less ACF with 4 aberrant crypts, relative to SSO/soy- (P < 0.01) and SSO/RS-fed rats (P < 0.05) in the distal colon. Body weight and food intake.
The final body weights did not differ among groups, except for the SSO/RS group in which body weight was lower (366 g) than in all fish oil–fed groups (FO/soy 455, FO/-cell 430, FO/RS 425 g) and the SSO/soy group (415 g) (pooled SEM, 12 g, P < 0.05). Daily food intake was also reduced in the SSO/RS-fed rats, relative to all other groups except those fed FO/RS (P < 0.05) (Table 3
).
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The cecal water of rats fed RS and soy fiber was 35 and 20% more cytotoxic, respectively, than for those rats fed -cellulose (P < 0.001) (Table 3)
. The greatest difference in cecal water cytotoxicity was between the -cellulose–fed groups and the RS-fed groups (all P < 0.001). The FO groups had 7% greater cytotoxicity than the rats fed SSO (P < 0.05).
Cecal SCFA.
Cecal butyrate concentration (µmol/g) was highest in all rats fed -cellulose, which was 2.8 and 2 times that in RS- and soy fiber–fed rats, respectively (P < 0.001) (Table 3)
. The butyrate concentration was 41% higher in rats fed RS than in soy-fed rats (P < 0.05). In rats fed FO, cecal butyrate concentration was 24% greater than in those fed SSO (P < 0.001). The highest mean concentration of cecal SCFA was observed in RS-fed rats, which had at least twice the value of that concentration of SCFA in rats fed the other two fiber types (P < 0.001, Table 3
). However, the butyrate:SCFA ratio was highest in -cellulose–fed rats (1:7) and lowest in RS-fed rats (1:31), whereas the soy fiber–fed rats had a ratio of 1:17. Cecal butyrate concentration and ACF number in the total colon were negatively correlated (r = -0.32, P < 0.05) (Fig. 1
).
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Cecal ß-glucuronidase activity differed between the -cellulose fed groups and those consuming the two other fiber sources (P < 0.001, Table 3
). The specific activities in the ceca of rats fed -cellulose were 2 and 3.5 times those in soy- and RS-fed rats, respectively. Enzyme activity was 28% lower in rats fed FO than in those fed SSO (P < 0.001). ß-Glucuronidase specific activity and cecal water cytotoxicity were inversely related (r = -0.69, P < 0.001) (Fig. 2
).
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Cecal ATP concentration of RS-fed rats exceeded those of soy-fiber and -cellulose groups by 88 and 94%, respectively (P < 0.001, Table 3
). Cecal ATP concentration and ACF number in the total colon were positively correlated (r = 0.28, P < 0.05) with a more pronounced relationship in the distal colon (r = 0.38, P < 0.01) (data not shown).
Cecal contents, fecal fat and fecal output.
The wet weight of cecal contents in RS-fed rats was 4 times higher and those in soy fiber–fed rats nearly 3 times higher than in the rats fed -cellulose (P < 0.001). The fecal fat concentration in rats fed SSO in combination with RS was greater than for all other dietary groups (P < 0.001) (Table 3)
. Fecal fat concentration correlated positively with the number of distal ACF (r = 0.338, P < 0.01). Fecal output in the rats fed soy fiber was at least 4 times greater than that in the other two fiber groups, which did not differ (P < 0.001).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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-cellulose showed the greatest level of protection against ACF formation, whereas RS or soy fiber in combination with SSO showed little protection. This was particularly evident in the distal colon, where RS was associated with the highest ACF count. In the proximal colon, rats fed soy fiber had the highest number of ACF. The ACF data were supported by other putative markers of cancer risk such as cecal water cytotoxicity, cecal SCFA concentrations (including butyrate), ß-glucuronidase activity, as well as cecal ATP and fecal fat concentrations. These may provide measures relating to possible mechanisms of promotion or inhibition of ACF expression, used here as a marker of cancer risk.
The relative protection against ACF formation associated with -cellulose, an insoluble and slowly fermentable fiber source, was associated with a reduction in cecal water cytotoxicity and increased cecal concentrations of butyrate and ß-glucuronidase activity. The inverse correlation between cecal butyrate concentration and number of ACF suggests an important mechanism of protection against neoplasia. Butyrate has been previously associated with reduced ACF and tumor formation (20
,51
) and has been shown to induce apoptosis in HT-29 colon cancer cells in vitro (22
,52
). Increased levels of colonic butyrate, as observed in wheat bran-fed rats, has also been associated with increased apoptosis as well as suppressed ACF formation (21
).
Microbial fermentation of dietary fiber and the resulting products in the cecum may play a role in modulating cancer risk further along the colon. In this study, fermentation events were identified using total SCFA production, ATP concentration and cecal bulk as putative indicators. It has been suggested that colonic fermentation of certain fiber sources, such as RS, could be beneficial because SCFA are generated and among them, butyrate is significantly protective (15
,53
,54
). The butyrate to SCFA ratio was lower in the rats fed RS (1:31) than in those fed soy fiber (1:18) or -cellulose (1:7). Even though RS-fed rats had the highest concentration of total SCFA and quantity of butyrate, the large cecal bulk in these rats may have acutely diluted the butyrate, and as a result, this diet was associated with reduced protection against ACF formation. This suggests that any antineoplastic effects associated with the -cellulose diets are more likely to be due to the butyrate produced, rather than the other SCFA measured. The fermentation stimulated by RS appears, therefore, to have little protective effect against ACF.
Soy fiber–fed rats had the greatest risk of colon cancer in the proximal colon and this corresponded with a reduced cecal butyrate concentration and increased cecal water cytotoxicity. Interestingly, the cecal bulk in the soy fiber–fed rats was less than that seen in RS-fed rats, suggesting that other cancer-promoting agents, independent of fermentation, may have been generated in the ceca in association with soy feeding. Soy protein relative to casein was found previously to increase damage and cell proliferation in the colon epithelium of rats, possibly through increased free fatty acid production in the colon (29
). This was interpreted as increasing the potential risk of colon cancer in this species. Recent studies with soy protein isolate have not shown significant differences from casein in cancer expression, (55
,56
). Some legumes in diets have been associated with less protection, as evidenced when rats were fed defatted soybean or chickpeas relative to an AIN casein control diet with a high fat content (30
,31
). This suggests that leguminous fiber or associated factors may be responsible. It is possible that components along with the fiber in soy may influence carcinogenesis, possibly due to release of noxious agents from bound forms (57
).
An interesting observation in this study was the inverse correlation between cecal water cytotoxicity and cecal ß-glucuronidase enzyme activity. Researchers have previously proposed that increased ß-glucuronidase activity is associated with a higher risk in models of colon cancer (41
,44
). The enzyme can liberate toxic or mutagenic compounds (bound by glucuronide bonds), which may have an undesirable influence on colonic health (58
). However, the enzyme has also been shown to be associated with the release of beneficial phytochemicals, such as lignans, which may provide protection (40
). An inverse correlation between cecal ß-glucuronidase activity and colonic adenomas was shown recently in rats fed wheat aleurone flour, a rich source of dietary fiber, including -cellulose (59
). Observations in the -cellulose–fed rats from the present study support this observation, implying a possible protective role for the ß-glucuronidase enzyme, as proposed by Jenab and Thompson (40
). However, further investigation is necessary to ascribe a specific mode of action to this enzyme.
In the distal colon, the number of ACF correlated directly with markers of fermentation in the cecum, such as SCFA concentration and ATP concentration. It is possible that very active cecal fermentation is not beneficial for the prevention of carcinogenesis. However, Govers et al. (25
) showed that feeding pigs RS with wheat bran displaced the fermentation site from the cecum to further down the colon, resulting in increased butyrate concentration and, therefore, potentially greater protection distally.
In the present study, a significant correlation occurred between fecal fat concentration and distal ACF number. A high fecal fat concentration has previously been associated with an increased colon tumor incidence (30
). This may also be associated with an increased concentration of fecal free fatty acids and secondary bile acids in the colons of rats, although the latter were not measured in this study. Such measures have been associated with increased risk of colorectal cancer (31
,60
) and may explain the greater number of ACF, particularly in the rats fed RS and SSO. Whether factors such as the high degree of cecal fermentation, increased cecal water cytotoxicity and increased fecal fat concentration act synergistically or separately to enhance ACF formation requires further clarification.
When comparing different fat sources used in this study, FO, high in (n-3) PUFA, was significantly more protective against ACF formation than SSO, with its high (n-6) PUFA content. The inhibitory effect of FO against colon carcinogenesis is supported by several studies. Epidemiologic studies provide strong evidence for the role of FO in colon cancer prevention. There is, for example, an inverse correlation between FO consumption and colon cancer risk identified from data from 24 European populations (61
). Rat colon cancer models generally support a protective role for FO, and one of these studies observed tumor prevention in response to FO feeding during initiation and postinitiation (34
,35
,62
). This corresponded to an increase in tumorigenesis with feeding a high corn oil diet during postinitiation, whereas corn oil had no effect when fed during initiation (35
). A possible mechanism to explain the anticancer role of (n-3) PUFA could be their ability to suppress inflammation by down-regulating the cyclooxygenase (COX)-2 enzyme, which is involved in the synthesis of proinflammatory prostaglandins. COX-2 activity is enhanced in experimental rat studies in response to feeding large amounts of (n-6) PUFA (36
). COX-2 has been detected in human colon tumors and in chemically induced colon tumors in rats (63
). An association between down-regulation of COX-2 expression and apoptosis has been identified in human colon cancer cells in vitro, suggesting this as a possible mechanism for the antineoplastic role of fish oil (64
). Feeding normal rats a diet high in (n-3) PUFA has been shown to suppress colonic cell proliferation and increase the number of cells undergoing apoptosis or differentiation, which could effectively control neoplasia (37
,38
). Another possible mechanism, which may explain the protection against colon cancer during the initiation phase, is the postulated ability of (n-3) PUFA to increase the rate of detoxification of AOM in the liver. This could decrease delivery of its metabolite, methylazoxymethanol (the DNA-alkylating and thereby cancer causing molecule), to the colon via the bloodstream, which would reduce AOM-induced colon carcinogenesis (35
).
The interactive effects of different fat and fiber sources on the incidence of colon cancer are complex and consideration of these is important for elucidation of mechanisms. It is possible that dietary fats are bound by fiber to a variable degree, depending on the structural properties of the fiber, and this may reduce the possibility of any adverse effects associated with high dietary fat. Similarly, it is possible that some fibers could be inhibited from exerting their effects on carcinogenesis due to the presence of fat. There may also be synergistic activity in inhibition of carcinogenesis between dietary fat and fiber. For example, FO has been shown to alter microflora populations of the colonic lumen, relative to corn oil feeding (65
). This alteration may affect the extent of dietary fiber fermentation by the appropriate microflora and therefore modulate the amount SCFA generated and also chemicals, some of which may be protective against colon carcinogenesis (37
). This is clearly a complex issue and requires further investigation.
We examined the extent to which fiber could counteract the effect of fat in rats fed a high fat "Western-type" diet. The minimum fiber proportion required in the diet to offset the potentially harmful fat effect appears to be 8 g/100 g (66
). -Cellulose was most effective in this respect, whereas the other two fiber sources were minimally protective. -Cellulose in combination with fish oil provided more protection in the early stages of colon carcinogenesis in rats, compared with RS or soy fiber in combination with sunflower seed oil.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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3 Abbreviations used: ACF, aberrant crypt foci; AOM, azoxymethane; COX, cyclooxygenase; DHA, docosahexaenoic acid; FO, fish oil; PUFA, polyunsaturated fatty acids; RS, resistant starch; SCFA, short-chain fatty acids; SSO, sunflower seed oil.
Manuscript received 29 October 2001. Initial review completed 10 January 2002. Revision accepted 3 May 2002.
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LITERATURE CITED |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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