Effect of Conventional and Unconventional Dietary Fibers in Colon

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Effect of Conventional and Unconventional Dietary Fibers in Colon Carcinogenesis BANDARU S. REDDY, KENSHI

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WATANABE,

and HIDEKI

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MORI

American Health Foundation, Naylor Dana Institute for Disease Prevention, Valhalla, NY 10595

Epidemiologic and animal model studies sug gest a p r o t e c t i v e e f f e c t of c e r t a i n d i e t a r y f i b e r s against colon cancer. This p r o t e c t i o n by the d i e t a r y f i b e r s may be mediated through (a) the di lution of tumorigenic compounds i n the gut,(b) the binding of tumorigenic compounds to the f i b e r i n the gut, and (c) an i n d i r e c t e f f e c t on the meta bolism of carcinogens. Experiments were conducted i n animal models to study the e f f e c t of c e r t a i n non-conventional d i e t a r y f i b e r s on colon c a r c i n o genesis. Rats were fed the d i e t s c o n t a i n i n g al falfa, c i t r u s pulp, p e c t i n , wheat bran, undegraded carrageenan or cholestyramine and t r e a t e d with azoxymethane (AOM), 3,2'-dimethyl-4-aminobiphenyl (DMAB), or methylnitrosourea (MNU) to induce tumors. Animals fed the wheat bran or c i t r u s pulp and t r e a t e d with AOM or DMAB had a lower colon tumor incidence than d i d those fed the c o n t r o l d i e t and treated with r e s p e c t i v e carcinogens. Al falfa d i e t had no e f f e c t on AOM- or MNU-induced colon tumors, whereas the p e c t i n d i e t i n h i b i t e d ΑΟΜ-induced but not MNU-induced colon tumors. Animals fed the d i e t s c o n t a i n i n g undegraded c a r r a geenan or cholestyramine developed more AOM and/or MNU-induced colon tumors than d i d the r a t s fed the c o n t r o l d i e t . Thus, the p r o t e c t i v e e f f e c t of var ious d i e t a r y f i b e r s i n colon carcinogenesis de pends on the type of f i b e r fed, as w e l l as the type of carcinogen used to induce tumors.

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Current address: Kagoshima University School of Medicine, Kagoshima, Japan Current address: Gifu University School of Medicine, Gifu City, Japan

0097-6156/83/0214-0001$06.00/0 © 1983 American Chemical Society

Furda; Unconventional Sources of Dietary Fiber ACS Symposium Series; American Chemical Society: Washington, DC, 1983.

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UNCONVENTIONAL SOURCES OF DIETARY FIBER Rapid progress has been made i n basic concepts concerning carcinogenesis (_1>2^· There are agents which are genotoxic, which by d e f i n i t i o n i n t e r a c t with the gene to y i e l d an abnormal genetic m a t e r i a l and would be considered i n i t i a t i n g agents (3)· The second broad c l a s s of agents act by e p i g e n e t i c mechanisms and tend to i n c r e a s e the development of l e s i o n s i n i t i a t e d by genotoxic carcinogens. Thus, t h i s l i s t includes co-carcinogens which operate at the same time as genotoxic carcinogens and can a l t e r the metabolism of a genotoxic agent with an increased r a t i o of a c t i v a t i o n / d e t o x i f i c a t i o n m e t a b o l i t e s . Such agents can a l s o act as more c l a s s i c tumor promoters which e x h i b i t t h e i r e f f e c t a f t e r the a c t i o n of a genotoxic carcinogen. Current concepts of colon cancer e t i o l o g y stem from m u l t i d i s c i p l i n a r y research e f f o r t s based on three major approaches, namely: (1) the v a r i a t i o n i n incidence of colon cancer as a f u n c t i o n of area of residence, with p a r t i c u l a r regard to migrant population; (2) the changes i n incidence as a f u n c t i o n of time; and (3) d e t a i l e d l a b o r a t o r y s t u d i e s i n humans, i n animal models, and through i n v i t r o systems* The consistency of these f i n d i n g s suggests that environmental f a c t o r s i n g e n e r a l , and dietary f a c t o r s i n p a r t i c u l a r , play a dominant r o l e i n the development of colon cancer i n humans. Epidemiologic studies suggest that d i e t s p a r t i c u l a r l y high i n t o t a l f a t and low i n f i b e r and i n c e r t a i n vegetables as w e l l as high intake of beef are g e n e r a l l y a s s o c i a t e d with an i n c r e a s ed incidence of l a r g e bowel cancer i n man (4-10). Dietary f a t may be a r i s k f a c t o r i n the absence of f a c t o r s that are p r o t e c t i v e , such as use of high f i b r o u s foods and f i b e r (11,12). As an example, i n F i n l a n d , where the d i e t a r y intake of f a t i s s i m i l a r to many of the Western c o u n t r i e s and the f i b e r intake i s higher, the incidence of colon cancer i s lower than a l l of the Western countries. This b r i e f review evaluates current research on the r e l a t i o n between d i e t a r y f i b e r and large bowel cancer i n humans, i n c l u d i n g the use of animal models. This b r i e f review also presents an e v a l u a t i o n of the mechanism whereby c e r t a i n d i e t a r y f i b e r s i n c l u d i n g conventional and unconventional f i b e r s modify the r i s k f o r the development of colon cancer. C o r r e l a t i o n and Case-Control Studies C r o s s - n a t i o n a l c o r r e l a t i o n s between the incidence of colon cancer and d i e t a r y h a b i t s have been used to s e l e c t hypotheses f o r t e s t i n g i n c a s e - c o n t r o l and cohort s t u d i e s . These s t u d i e s have shown that c e r t a i n food preferences appear to be a s s o c i a t e d with e i t h e r a h i g h - or a l o w - r i s k f o r colon cancer. When such c o r r e l a t i o n s are supported by experimental evidence from animal s t u d i e s , the hypothesis could be a t t r a c t i v e . B u r k i t t (10,13) f i r s t observed the r a r i t y of l a r g e bowel cancer i n most A f r i c a n populations and suggested that populations consuming a d i e t r i c h i n f i b e r have a lower incidence of t h i s type of cancer, while those e a t i n g r e f i n e d carbohydrates


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Dietary Fibers in Colon Carcinogenesis

and l i t t l e f i b e r have a higher i n c i d e n c e . A recent study comparing low-risk populations i n Kuopio, F i n l a n d , with those at high r i s k i n Copenhagen i n d i c a t e d that d i e t a r y f i b e r intake i s higher i n F i n l a n d compared with Copenhagen (14). The F i n n i s h population i s unique i n t h i s respect because i n t h i s country the t o t a l d i e t a r y f a t i s s i m i l a r to countries with high rate of colon cancer. The c r u c i a l d i f f e r e n c e i n d i e t a r y intake between F i n l a n d and Denmark and other Western countries may r e l a t e to d i e t a r y f i b e r and meat. Our data a l s o suggest that one of the f a c t o r s c o n t r i b u t i n g to the low r i s k of large bowel cancer i n Kuopio appears to be that a high intake of d i e t a r y f i b e r (mainly c e r e a l f i b e r ) leads to increased s t o o l bulk, i n e f f e c t d i l u t i n g tumorigenic compounds i n the colon (12)· The r e s u l t s are cons i s t e n t with a p o s s i b l e r o l e f o r d i e t a r y f i b e r i n the prevention of colon cancer i n humans. Case c o n t r o l studies have been conducted to study the possi b l e r e l a t i o n of d i e t a r y f i b e r to large bowel cancer. Recently, Dales ejt a l . (15) found that among American blacks s i g n i f i c a n t l y more colon cancer p a t i e n t s than c o n t r o l s reported that t h e i r d i e t was high i n saturated f a t and low i n f i b r o u s foods. Inv e s t i g a t i n g many d i e t a r y c o n s t i t u e n t s , Modan et a l . (16) d i s covered that those c o n t r i b u t i n g l e s s to the d i e t s of p a t i e n t s with colon cancer than to the d i e t s of c o n t r o l s were those containing fiber. Bjelke (17) who interviewed hospitalized p a t i e n t s and c o n t r o l s i n Minnesota and i n Norway, learned that c o l o r e c t a l cancer p a t i e n t s l e s s f r e q u e n t l y ate vegetables, in p a r t i c u l a r the Minnesota p a t i e n t s ate l e s s cabbage. S i m i l a r l y , Graham et_ a l . (18) found that i n d i v i d u a l s who ate vegetables such as cabbage, b r o c c o l i and Brussels sprouts had a lower r i s k of colon cancer. These studies i n d i c a t e that d i e t s with a high intake of t o t a l f a t and a low intake of c e r t a i n f i b e r s and c e r t a i n vegetables are g e n e r a l l y a s s o c i a t e d with an increased incidence of colon cancer i n humans. Even i n populations consuming high amount of f a t , high d i e t a r y f i b e r acts as a p r o t e c t i v e f a c t o r i n colon c a r c i n o g e n e s i s . P o s s i b l e Mechanism of P r o t e c t i v e E f f e c t of D i e t a r y F i b e r In Colon Carcinogenesis Although the concept of f i b e r involvement i n colon c a r c i n o genesis i s a t t r a c t i v e , the data o f t e n appear c o n t r a d i c t o r y and confusing. Discrepancies may have a r i s e n from the general misuse of f i b e r terminology. As w e l l , experimental design has f a i l e d to account f o r the p o s s i b l e subtle e f f e c t of i n h i b i t o r s , e s p e c i a l l y i n r e l a t i o n to the promoting process. Evaluations of the b i o l o g i c f u n c t i o n of d i e t a r y f i b e r have often lacked comp l e t e information on the nature of the f i b e r . Dietary f i b e r comprises a heterogenous group of carbohydrates, i n c l u d i n g c e l l u l o s e , hemicellulose and p e c t i n , and a noncarbohydrate substance, l i g n i n (19). According to Van Soest (20), f i b e r s can be c l a s s i f i e d i n t o three groups: vegetable


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f i b e r s , which are h i g h l y fermentable and have l i t t l e i n d i g e s t i b l e residue; brans, which are l e s s fermentable; and chemically p u r i f i e d f i b e r s , such as c e l l u l o s e , which are r e l a t i v e l y nonfermentable. Pectins and gums, s o l u b l e substances that are not true f i b e r s , are considered part of the d i e t a r y f i b e r complex because of the s i m i l a r e f f e c t s they can e l i c i t i n the d i e t . Wheat bran and vegetable and f r u i t f i b e r s have d i f f e r e n t percentages of c e l l u l o s e , hemicellulose and l i g n i n . Carrageenan, a broad generic c l a s s of s u l f a t e d polysaccharides derived from a wide range of seaweed species, can be c l a s s i f i e d as non-conventional f i b e r and i s used i n food as an e m u l s i f i e r , s t a b i l i z e r , thickener and g e l l i n g agent. The p r o t e c t i v e e f f e c t of d i e t a r y f i b e r may be due to ads o r p t i o n , d i l u t i o n or metabolism of cocarcinogens, promoters and y e t - t o - b e - i d e n t i f i e d carcinogens by the components of the f i b e r (12,21,22). There i s evidence that a l f a l f a , wheat straw and some other f i b e r s can bind considerable amounts of b i l e acids i n v i t r o (23). This i n d i c a t e s that the d i f f e r e n t types of nonn u t r i t i v e f i b e r s possess s p e c i f i c binding p r o p e r t i e s . Dietary f i b e r could a l s o a f f e c t the enterohepatic c i r c u l a t i o n of b i l e s a l t s (24) which act as colon tumor promoters (6)· F i b e r not only i n f l u e n c e s b i l e a c i d metabolism (12,22) thereby reducing the formation of p o t e n t i a l tumor promoters i n the colon, but a l s o exerts a s o l v e n t - l i k e e f f e c t i n that i t d i l u t e s p o t e n t i a l carcinogens and cocarcinogens by i t s bulking e f f e c t (12) and i s able to bind b i l e acids and c e r t a i n carcinogenic compounds (23,25,26). On the other hand, d i e t a r y undegraded carrageenan markedly enhances the b i l e a c i d content i n the colon, thereby i n c r e a s i n g the p o t e n t i a l colon tumor promoters i n the gut ( 6 ) . Smith-Barbaro et a l . (26) i n our l a b o r a t o r y determined the c a p a c i t y of various f i b e r s to bind the colon carcinogen 1.2-dimethylhydrazine (DMH) in vitro. The percent of DMH bound to wheat bran, corn bran, a l f a l f a f i b e r and dehydrated c i t r u s pulp was dependent on pH of the medium as w e l l as the type of f i b e r examined. Results from t h i s study show that at c o l o n i c pH, a greater percent of DMH was bound by wheat bran than by c i t r u s pulp. Therefore, i t i s p o s s i b l e that c e r t a i n f i b e r s bind c a r cinogen at c o l o n i c pH, thus making i t u n a v a i l a b l e f o r contact with the c o l o n i c mucosa. Other f i b e r s such as p e c t i n ( s o l u b l e f i b e r ) do not bind DMH at c o l o n i c pH, but may modify the metabolism of carcinogen v i a a c t i v a t i o n / d e a c t i v a t i o n steps e i t h e r i n the l i v e r and/or i n the c o l o n i c mucosa. I n v e s t i g a t i o n s have been c a r r i e d out i n s e v e r a l l a b o r a t o r i e s to determine whether there are d i f f e r e n c e s i n f e c a l c o n s t i t uents between populations at high and low r i s k of colon cancer, and whether changes i n the f i b e r content of the d i e t would a l t e r the concentration of f e c a l b i l e acids that act as colon tumor promoters and the a c t i v i t y of f e c a l m i c r o f l o r a . Recently, we studied healthy i n d i v i d u a l s i n Kuopio, F i n l a n d , an area of low r i s k f o r the development of colon cancer (12). Dietary


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h i s t o r i e s i n d i c a t e d that the t o t a l f a t consumption i s s i m i l a r to that i n the United States but the intake of c e r e a l f i b e r i n F i n land i s higher and the d a i l y output of feces three times higher than that of healthy i n d i v i d u a l s i n the United S t a t e s . The conc e n t r a t i o n of f e c a l secondary b i l e a c i d s , mainly deoxycholic a c i d and l i t h o c h o l i c a c i d i s l e s s i n Kuopio than i n the United States, but the t o t a l d a i l y output i s the same i n the two popul a t i o n s because of the t h r e e f o l d greater d a i l y output of feces i n Kuopio. This suggests that increased f e c a l bulk d i l u t e s suspected carcinogens and promoters that may be i n d i r e c t contact with the large bowel mucosa. Cummings (27) demonstrated that f i b e r from c a r r o t , cabbage, apple, bran and guar gum produces d i f f e r e n t responses i n f e c a l weight i n humans r e l a t e d to the i n take of pentose-containing polysaccharides i n the f i b e r . The f e c a l weight increased by 127% when bran was added to the d i e t and 20% when guar gum was added; c a r r o t , cabbage and apple produced intermediate changes. In another study, Cummings (28) reported that an increase i n c e r e a l f i b e r intake from 17 to 45 g/d increased the f e c a l weight from 79 to 228 g/d and d i l u t e d the f e c a l b i l e a c i d s . Kay and Truswell (29) showed that adding wheat f i b e r to the d i e t decreased the concentration of f e c a l b i l e acids and n e u t r a l s t e r oids because of the bulking e f f e c t of f i b e r , whereas the a d d i t i o n of p e c t i n to the d i e t increased the f e c a l s t e r o i d and b i l e a c i d output. These r e s u l t s suggest that the e f f e c t on f e c a l b i l e a c i d e x c r e t i o n may depend on the type of f i b e r consumed. The e f f e c t of d i e t a r y wheat bran and a l f a l f a at 15% l e v e l on the composition of f e c a l b i l e acids was studied i n r a t s fed a s e m i p u r i f i e d d i e t (30). Diets containing wheat bran and a l f a l f a caused a s i g n i f i c a n t increase i n s t o o l weight. The concentrat i o n of f e c a l b i l e a c i d s , p a r t i c u l a r l y hyodeoxycholic acid, p-muricholic a c i d , deoxycholic a c i d and l i t h o c h o l i c a c i d was lower i n r a t s f e d wheat bran, compared to those f e d a c o n t r o l d i e t , b u t the d a i l y output of these b i l e acids was the same i n both groups. A l f a l f a had no e f f e c t on the concentration of f e c a l b i l e a c i d s , but the d a i l y e x c r e t i o n of deoxycholic a c i d , l i t h o c h o l i c a c i d and 1 2 - k e t o l i t h o c h o l i c a c i d was increased compared to the c o n t r o l d i e t . I t i s apparent from t h i s study that the f e c a l e x c r e t i o n of b i l e acids v a r i e s with the type and amount of d i e t a r y f i b e r . U n t i l r e c e n t l y , the nature of the carcinogens responsible f o r c o l o n cancer not only was obscure, but there were no r e a l leads. Because of p o t e n t i a l importance of f e c a l mutagens i n the genesis of l a r g e bowel cancer and of p o s s i b l e r o l e of d i e t a r y ^ f a c t o r s i n the i n d u c t i o n of colon cancer, the f e c a l mutagenic a c t i v i t y of various population groups with d i s t i n c t d i e t a r y habits and v a r i e d colon cancer incidences was determined by several investigators. E h r i c h jet a l . (31) have demonstrated that the s t o o l s of South A f r i c a n urban whites who consume a h i g h - f a t , l o w - f i b e r d i e t and who are at high r i s k f o r colon


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UNCONVENTIONAL SOURCES OF DIETARY FIBER cancer development were higher (17% of the i n d i v i d u a l s ) i n mutagenic a c t i v i t y with Salmonella typhimurium s t r a i n s TA98 and TA100 without microsomal a c t i v a t i o n compared to South A f r i c a n urban and r u r a l blacks (0-5% of the i n d i v i d u a l s ) who consume a low-fat, h i g h - f i b e r d i e t and who are at l o w - r i s k . Bruce et a l . (32) were the f i r s t to show that the feces of some normal humans consuming a h i g h - f a t , l o w - f i b e r d i e t contained compounds that caused d i r e c t mutagenesis of TA98 and TA100 i n the Ames assay. They have a l s o demonstrated that increased d i e t a r y fiber, -tocopherol or v i t a m i n C reduced f e c a l mutagens. Kuhnlein et a l . (33) compared f e c a l mutagens (water e x t r a c t s ) from a group of vegetarians consuming h i g h - f i b e r d i e t s with those from persons on t y p i c a l North American d i e t s c o n t a i n i n g meat. On TA100 and TA98, ovo-lactovegetarians and s t r i c t vegetarians had lower l e v e l s of f e c a l mutagens than non-vegetarians. Correlation studies between the pH of the f e c a l homogenate and mutagenicity i n d i c a t e the presence of s e v e r a l f e c a l mutagens. Recently, we have s t u d i e d f e c a l mutagens of 3 populations with d i s t i n c t r i s k f o r the development of colon cancer, a highr i s k population i n New York (non-SDA) consuming a h i g h - f a t , lowf i b e r , mixed-Western d i e t , a low-risk v e g e t a r i a n SDA (SeventhDay A d v e n t i s t s ) and a l o w - r i s k population i n Kuopio, F i n l a n d consuming a h i g h - f a t , h i g h - f i b e r d i e t (34). F e c a l samples of non-SDA were h i g h l y mutagenic i n TA98 without microsomal a c t i v a t i o n , followed by TA100 without a c t i v a t i o n and TA100 with a c t i vation. None of the samples of SDA tested showed mutagenic a c t i v i t y i n any of the t e s t e r systems, whereas Kuopio samples e x h i b i t e d a c t i v i t y only i n TA98 with microsomal a c t i v a t i o n . Animal Model Studies i n Colon Carcinogenesis; E f f e c t of Conventional and Unconventional F i b e r s Research on the mechanisms of cancer causation i n the large bowel has been a s s i s t e d by the discovery of s e v e r a l animal models that m i r r o r the type of l e s i o n s seen i n man. These models i n c l u d e (a) i n d u c t i o n of l a r g e bowel cancer i n r a t s through chemicals such as 3-methyl-4-aminobiphenyl, or 3-methyl2-naphthylamine; (b) d e r i v a t i v e s and analogs of c y c a s i n and methylazoxymethanol (MAM) such as azoxymethane (AOM and 1,2-dimethylhydrazine (DMH), which work w e l l i n r a t s and mice of s e l e c t e d s t r a i n s ; and (c) i n t r a r e c t a l a d m i n i s t r a t i o n of d i r e c t a c t i n g carcinogens of the type of a l k y l n i t r o s o u r e a s , such as methylnitrosourea (MNU) or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) which lead to cancer of the descending colon i n every species tested so f a r . The r e l a t i o n between d i e t a r y f i b e r consumption and c o l o n cancer has been s t u d i e d i n experimental animals. Wilson et_ a l . (35) found that Sprague-Dawley r a t s fed a d i e t c o n t a i n i n g 20% corn o i l or beef f a t and 20% wheat bran had fewer benign colon tumors induced by DMH given by g a s t r i c i n t u b a t i o n than rats fed a c o n t r o l d i e t c o n t a i n i n g 20% f a t and no bran. It i s possible that with a d d i t i o n a l time, a number of tumors that were c l a s s i -


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REDDY ET AL.


f i e d as benign might have developed a more i n v a s i v e c h a r a c t e r . There was no d i f f e r e n c e i n the incidence of colon cancer between the r a t s fed corn o i l and those fed beef f a t . In another study, Clapp et^ a l . (36) found that DMH-induced colon tumors were i n creased i n BALB/C mice fed a semisynthetic d i e t c o n t a i n i n g 5% f a t and 20% W/W corn bran, soybean bran and s o f t winter wheat bran. DMH-induced colon tumor incidence i n mice fed the c o n t r o l d i e t was s u r p r i s i n g l y low, about 12%. In these s t u d i e s , the experimental d i e t s c o n t a i n i n g high-fat/no bran and h i g h - f a t / h i g h bran, (35) or low-fat/no-bran and low-fat/high bran (36) d i f f e r ed s u b s t a n t i a l l y i n c a l o r i c d e n s i t y . Animals on high bran d i e t s might have consumed q u a n t i t a t i v e l y d i f f e r e n t l e v e l s of vitamins and minerals compared to those fed high fat-no bran d i e t or low fat-no bran d i e t s because the r a t s adjust t h e i r food intake to compensate f o r n o n - d i g e s t i b l e f i b e r i n high bran d i e t . It i s a l s o p o s s i b l e that c e r t a i n f i b e r s may cause abnormal h i s t o l o g y and damage to c o l o n i c mucosa, thereby a l t e r i n g the a b s o r p t i v e c a p a c i t y of the i n t e s t i n a l t r a c t as w e l l as b i l e a c i d - b i n d i n g c a p a c i t y (37,38) which have bearing on colon c a r c i n o g e n e s i s . A recent study by F l e i s z e r et_ a l . (39) i n d i c a t e d that the incidence of colon tumors induced by DMH i n r a t s decreases as the d i e t a r y intake of f i b e r i n c r e a s e s . The number of animals used i n t h i s study was small. The d i e t s i n that study, namely high bran d i e t (28% f i b e r ) , s p e c i a l chow (15% f i b e r ) , r a t chow (5% f i b e r ) F l e x i c a l d i e t (0% f i b e r ) d i f f e r e d not only i n c o n s i s tency (that i s , s o l i d or l i q u i d ) but a l s o i n the proportions of p r o t e i n and f a t s , which have been shown to have an independent e f f e c t on colon carcinogenesis induced by DMH. However, the col o n cancer incidence i n f i b e r - f r e e ( F l e x i c a l ) group was lower than i n r a t chow group. Some r e d u c t i o n i n tumor incidence i n the r a t s i n g e s t i n g a h i g h - f i b e r d i e t might be expected on the b a s i s of reduced energy i n t a k e . Although the study's f i n d i n g s suggest that reduced intake alone cannot account f o r the s i g n i f i c a n t p r o t e c t i v e e f f e c t of d i e t a r y bran, a b e t t e r experimental design might have strengthened the r e s u l t s . In another study, Cruse e_t a l . (40) found that a d i e t cont a i n i n g 20% wheat bran had no e f f e c t on colon carcinogenesis i n duced by DMH i n r a t s . Not only were the number of animals used i n t h i s study small (10 r a t s / g r o u p ) , but a l s o the doses of the chemical i n t h e i r experiment were so high (40 mg/kg body weight/week f o r 13 weeks) that any p r o t e c t i v e e f f e c t of bran might have been unobservable. In a study of the e f f e c t of d i e t on chemical c a r c i n o g e n e s i s , i t i s important to avoid exposing the animal to an excessive l e v e l of carcinogen f o r a long p e r i o d , as t h i s may obscure more subtle changes induced by c e r t a i n d i e t a r y modifications. In a d d i t i o n , d i f f e r e n c e s i n c a l o r i c density of experimental d i e t s a t t r i b u t a b l e to the d i l u t i o n a l e f f e c t of added f i b e r f u r t h e r complicated the i n t e r p r e t a t i o n of the data. In f a c t , the data presented by Cruse et a l . ( 4 0 ) suggest that a h i g h - f i b e r d i e t reduces the frequency of death due to DMH i n rats.


7

8

UNCONVENTIONAL

SOURCES

OF

DIETARY

FIBER

The e f f e c t of a d i e t c o n t a i n i n g 15% a l f a l f a , p e c t i n or wheat bran on c o l o n carcinogenesis by MNU or AOM was studied i n F344 r a t s by Watanabe et a l . (41). In t h i s study, the e x p e r i mental d i e t s were not adjusted i s o c a l o r i c a l l y . The a d d i t i o n of p e c t i n or wheat bran to the d i e t g r e a t l y i n h i b i t e d colon tumor incidence induced by AOM, a carcinogen r e q u i r i n g host-mediated metabolic a c t i v a t i o n (Table I)· However, the incidence of AOMinduced colon tumors was not i n f l u e n c e d by the a d d i t i o n of a l f a l f a to the d i e t . The d i e t s c o n t a i n i n g wheat bran and p e c t i n d i d not protect against MNU-induced colon c a r c i n o g e n e s i s . Table I Colon Tumor Incidence i n Female F344 Rats Fed D i e t s Containing P e c t i n , A l f a l f a , or Wheat Bran and Treated with Azoxymethane or Methylnitrosourea

% Animals Colon Tumors Diet

Azoxymethane treated 57 10 53

Control Pectin Alfalfa Wheat Bran a

a

33a

S i g n i f i c a n t l y d i f f e r e n t from the groups or a l f a l f a d i e t by X t e s t , P

Effect of Conventional and Unconventional Dietary Fibers in Colon

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