[CANCER RESEARCH 38, 2912-2917, September 1978]
0008-5472/78/0038-0000$02.00
A Double-Blind Study on the Effect of Purified Cellulose Dietary
Fiber on 1,2-Dimethylhydrazine-induced Rat Colonic Neoplasia'
Hugh J. Freeman,2 Gene A. Spiller, and Young S. Kim3
Gastrointestinal Research Laborato,y, veteran's Administration Hospital and unh,rsity
Laboratories, Palo Alto, California 94304
of California, San Francisco, California 94121, and Syntex Research
methylhydrazine. These findings were then extended to
another cycasin analog, azoxymethane (24), as well as to
The incidence,distribution,size, and histopathobogy
of other animals including mice and hamsters (20, 21). Not
grosslyvisible colonictumors inducedby parenteral ad only are these cycasin analogs highly effective and reliable
ministrationof I ,2-dimethylhydrazinewere examined in as carcinogenic agents, but the colonic tumors caused by
rats fed either a chemically defined fiber-free diet or a them appear to be remarkably similar to human neoplasms
nutritionallyand calorically equivalent diet containinga (6, 16, 23). Since colonic cancer in humans is generally
purifiedfIber component,microcrystallinecellulose.This thought to have a dietary etiology (8), these animal models
double-blindstudyindicatesthat cellulose ingestionwas have been used to investigate the potential role of specific
associated with reduced numbers of animals involved dietary alterations in cobonic neoplasia development.
with colonicneoplasiaas well as a reductionin the total
Epidemiological studies in humans have suggested that
numbersof colonictumors. Furthermore,this protective one dietary factor predisposing to cobonic cancer is fiber
effect of cellulose appears to be time dependent and deficiency (2, 3, 9, 15). Studies with experimental animals,
associated with a shift in tumor distribution from the proxi
however, have provided apparently conflicting information
mal colon to a more distal site. Cellulose fiber had no (25, 27). In one (25), the number of cobonic neoplasms
apparent effect on colonictumor size, histopathology,or remained unchanged despite addition of cellulose in large
the incidence of other tumors known to occur In this quantities to a control semisynthetic diet. In the other (27),
experimentalanimal model. This studystronglysupports significantly reduced numbers of cobonic neoplasms oc
the hypothesisthat fiber is an importantprotectiveagent curred in rats fed wheat bran, a nonpurified fiber-containing
against colonicneoplasiadevelopment.While the mach mixture, although the percentage of animals with invasive
anism for this protective effect remains obscure, it ap or metastatic adenocarcinomas was similar. This discrep
pears to be temporallyrelatedto the durationof fiber ancy might have been due to qualitative or quantitative
ingestion as well as to a differential fiber effect on either differences in 1 or more administered specific fiber com
the luminal content or the mucosa of the proximal and ponents (or nonfiber components) or to relative differences
distalcolon.
in the food intake and nutritional status of the animals.
In this double-blind study, the effect of 1 specific dietary
INTRODUCTION
fiber component, microcrystalline cellulose, on dimethyl
Coboniccancer is a major cause of cancer mortality and hydrazine-induced colonic neoplasia was examined in rats
the beadingcause of morbidity and mortality from gastroin fed chemically defined diets. The results provide strong
testinal cancer in North America (22). In the past informa evidence that cellulose fiber is protective against the devel
tion related to diagnosis and treatment of this disorder has opment of colonic neoplasia in an experimental animal
been limited to clinical observation. However,the develop model.
ment of various experimental models of cobonic cancer
have provided another means of examining some of the MATERIALS AND METHODS
questions raised regarding etiology and pathogenesis.
Animals and Diets. Six-week-oldmale Wistar rats (Si
In 1963 Laqueuretal. (11) first reported the induction of
monsen
Laboratories, Inc., Gilroy, Calif.) weighing 100 to
colonic neoplasms in rats with cycad meal. Later, cycasin
120
g
and
previously maintained on standard laboratory
and its aglycone, methylazoxymethanol, were found to be
chow
pellets
(Ralston Purina Co., St. Louis, Mo.) were
effective (10). In 1967 Druckrey et al. (5) induced cobonic
randomly
assigned
in pairs to separate cages. Water was
neoplasia in rats with a synthetic cycasin analog, 1,2-di
supplied ad libitum at all times. Specially designed food
containers (Lithgow Manufacturers, San Mateo, Calif.) con
, SupportedbyUSPHS
GrantCA-14905
fromtheNationalCancerInstitute sisting of an open-topped glass jar equipped with a wtre
through the National Large Bowel Cancer Project and by a Veteran's
mesh insert to prevent food spillage were securely attached
Administration Research Grant.
inside
animal cages. Two groups of 30 rats each, randomly
a Recipient of a fellowship from the Medical Research Council of Canada,
chosen, were fed 1 of 2 different color-coded, chemically
Ottawa, Ontario, Cenada.
defined isocaboric diets for the remainder of the study
Research Laboratory (151M2), Veterans Administration
Hospital, 4150 Clem
(Table 1). Both basic diets were prepared by mixing in a
ent Street, San Francisco, Calif. 94121.
Hobart blender. The fiber-containing diet was then pre
Received February 16, 1978; accepted June 6, 1978.
ABSTRACT
S To
whom
2912
requests
for
reprints
should
be
addressed,
at
Gastrointestinal
CANCERRESEARCH
VOL.38
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Dietary Cellulose Fiber and Colonic Neoplasia in Rats
Table 1
pared by addition of a highly purified microcrystalline
cellulose. Each diet was packaged, marked with the appro
priate color code, and stored as a dry powder at 45°
until use. No other fiber components (hemicellubose, lignin,
pectin, mucilages) were found in either diet with dietary
fiber analysis (Table I).
Composition
of rat diets administered
dietFiber-free
of total
[email protected]
Ingredients%
Carcinogenesls. Each group consistedof 10 control
dietFiber
powder6.956.66Saffboweroil
white
anjmals and 20 carcinogen-treated animals. Animals receiv
ing carcinogen were given once-weekly s.c. injections of
1,2-dimethylhydrazine dihydrochboride (Aldrich Chemical
Company, Inc., Milwaukee, Wis.) for 16 weeks at a dosage
of 25 mg/kg. This was prepared as a 0.5% solution in 1 mM
EDTA (Mallinckrodt Chemical Works, St. Louis, Mo.) ad
justed to pH 6.5 with sodium bicarbonate. Controls received
an equivalent amount of EDTA at identical pH. Preliminary
studies in a separate group of rats had established this as
an effective regimen in our laboratory for cobonic tumor
induction. The color-coded diets were given for 2 weeks
prior to the first injection to ensure adequate and compa
rable intake prior to carcinogenesis.
4.50Vitaminmix―1.000.95Cornstarch
4.807.60
Mineralmix@@8.00
Total dietary fjber@@
4.50
0
(0)69.13
(4.50)Total
(cellubosee)72.30
ingredients100.0100.0
a Casein (HCI); edible extra grade hydrochloric acid casein, 30
to 40 mesh; Milk Products Ltd., Sydney,Australia.
b Mineral
mix
USP
XVIII (Teklad,
ARS/Sprague-Dawley
Corp.,
Madison, Wisc.) contained (g/100 g of mix): sodium chloride,
13.93; potassium biphosphate, 38.90; anhydrous magnesium sul
fate, 5.73; calcium carbonate, 38.14; ferrous sulfate, 2.70; man
ganesesulfate,
0.401
;potassium
iodide,
0.079;
zincsulfate,
0.0548;
cupric
Balance and Weight Studies. Following6 weeksof diet
sulfate,
0.0477; cobaltous
chloride,
0.0023. Selenium,
fluo
ride, and chromium were not present.
administration and 4 weeks after the initiation of the injec
tion schedule, individual intakes, outputs, and weight gains
of 6 animals, randomly chosen from each group, were
measured; a metabolic balance cage housed each rat sap
arately (Table 2). In addition, animals were weighed weekly
immediately before injection of either the carcinogen or
control solution. Finally, the animals were weighed imme
diately prior to sacrifice (Table 3).
C Vitamin
mix
AOAC
(Teklad,
ARS/Sprague-Dawley
Corp.)
con
tamed (per 100g of mix): vitamin A, 200,000IU; vitamin D, 20,000
IU; vitamin E, 1000 IU; menadione, 0.05 g; choline, 20.0 g; p
aminobenzoic
acid, 1 .0 g; inositol,
1 .0 g; niacin,
0.4 g; calcium
D
pantothenate, 0.4 g; riboflavin, 0.08 g; thiamin-HCI, 0.05 g; pyri
doxine-HCI,0.05 9; folic acid, 0.02 g; biotin, 0.004 g; vitamin B12,
0.0003g.
d Dietary
fiber
analysis
lose, KMnO4 lignin,
for cellulose,
water-insoluble
pectic substances,
and mucilages
hemicellu
is based on
data from analysis by J. B. Robertson, Cornell University, Ithaca,
N. V., and D.A.T. Southgate, Medical Research Council, Cam
bridge, England. Only cellulose fiber component was present.
NecropsyStudies.Ratswere randomlysacrificedbegin
ning 4 weeks after the final injection of 1,2-dimethylhydra
zine dihydrochboride (28 weeks of age). During each 4-week
time interval for the following 24 weeks, 3 or 4 rats from
e Avicel,
PH-105 cellulose
edible flour,
F.M.C. Corp.,
Philadel
phia, Pa.
Table2
Metabolic
balance study
Totals over 1
wk/groupFood
intakeWater
outputDiet
group(9)(ml)(ml)(g)Wt
(g)Fiber-free
diet
±7.20
Fiberdiet112.2
intakeUrine
gain
±9.7
±37.9
104.2 ±6.7165.3 150.0 ±17.379.3
±0.95
±26.8
53.3 ±11.32.789.22 ±1•18b24.729.0
a Mean ± S.E. ; n = 6 carcinogen-injected
rats/group.
b
(t test versus control
fiber-free
diet group) <0.005.
@
outputStool
Other
values
not statistically
±6.8
different.
Table3
Meanweights of carcinogen-injectedrats
Wt(g)
wt gain on
Diet groupInitial
sacrificeFiber-free
injectionFinal
diet166.8
14,5@'Fiberdiet161.8
injectionMean
±8.9a233.9
±9.3207.3
±2.6k'400.6
±2.2369.5
a Mean ±S.E. ; n = 20 carcinogen-injected
b Mean
(fiber-free
± S.E.
at sacrifice
diet group,
carcinogenWt
excluding
at
±7.60496.4
±8.7439.1
±
±19.4@'
rats/group.
animals
n = 18; fiber diet group,
dying
in each
n = 14). Animals
group
dying
prior
to sacrifice
before sacrifice
weighed considerably less relatedto tumor complications, postmortemdehydration, and
cannibalism.
C p
SEPTEMBER1978
(t
test
versus
fiber-free
control
diet
group)
<
0.05.
2913
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H. J. Freeman et a!.
@
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each group were autopsied. A rat found dead during any
time period was included in that group. In total, 80% of the
carcinogen-treated and all control-injected rats underwent
sacrifice. The presumptive cause of death was recorded for
rats dying prior to sacrifice. All rats, including those dying
prior to sacrifice, were autopsied. Proximal (ascending
colon and cecum) and distal (descending colon and rectum)
cobonic neoplasms were enumerated and measured for size
and distribution. In addition to colonic neoplasms, a careful
examination
of the remaining
gastrointestinal
@
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tumor metastases.
.%-
a)
In
.@ o o
+1+1
C@
0
W
tract, thorax,
and abdomen was undertaken for additional
@
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@io o
.@ +1+1
.0
c'@
°°
°°
tumors or
.!@
Results were recorded on a predesigned
form . Intestinal neoplasms as well as segments of representative normal-appearing proximal and distal colon were
oriented on mesh, placed in separate vials containing either
10% neutral phosphate-buffered
formalin or modified
Bouin's fixative (750 ml aqueous saturated picric acid, 250
ml 38% formaldehyde, and 10 ml glacial acetic acid),
embedded in paraffin, and sectioned at 5 @m.Multiple
serial sections were obtained from most tumors and stained
with hematoxylin and eosin.
Tumors were classified histologically according to the
criteria of Ward et a!. (23, 24) as either polypoid neoplasms
or adenocarcinoma (including the mucinous type). Evidence of invasion into or beyond the tunica muscularis was
required to label the tumor as an adenocarcinoma. As in
Ward's classification (23, 24) stalk invasion was demonstrable in some polypoid neoplasms.
Statistical Analysis. At the conclusion of the study,
collected data were analyzed statistically with the x2 and
Student's t tests, results were recorded, and finally dietary
composition was revealed.
.@
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‘@
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+1+1
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00
RESULTS
o
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Diet Analysis.The chemicalcompositionsof both diets
@
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@
are shown in Table 1. Except for the highly purified microcrystalline
cellulose
(4.5g/100 g of dietby weight)inthe
fiber-containing diet, other fiber components (hemicelbulose, pectin, lignin, mucilages) were not present.
@
Balance and Weight Studies. Resultsare shown in Ta-
@
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bles 2 and 3. Carcinogen-injected rats (n = 20/group) were
not statistically different from their respective control
groups (n = 10/group). Of all parameters examined during
the course of the metabolic balance study, only mean stool
weights were significantly greater in the cellulose fiber diet
@
group
@
@
@
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tended to weigh less and to gain less weight compared to
the fiber-free diet group. However, this difference was never
statistically significant at any time interval during carcinogenesis. At sacrifice mean weights (±S.E.) of non-tumorbearing rats from the fiber-free group (481.7 ±13.0 g) and
the fiber diet group (444.3 ±13.0 g) were not statistically
different from those of all animals at sacrifice in either
group.
@
@
@
@
@
i
@I()
.@o;
(p < 0.005). Animals
in the cellulose
fiber
+1+1
@,
.@
.@
‘@
:!
.@
E
,@ (°
@,
.@ 0 o
E
+‘
,@ ‘@ C
.@
group
Carcinogenesisand Necropsy Studies. All 20 control
animals from both diet groups were sacrificed. Spontaneous colon tumors are rare in untreatedrats(14).As
anticipated with the number of animals used, no control
was found to have a detectable neoplastic lesion. Without
preselection of obviously ill animals, 80% of all carcinogen2914
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w
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E °
<
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.
.@‘Z
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.@
<
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2
..@6 ‘@
a
tZ iZ
CANCER RESEARCHVOL. 38
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Dietary Cellulose Fiber and Co!onic Neoplasia in Rats
ogen-treated animals at specific sites as well as mean
number of tumors per animal in each group. The percent
age of rats with detectable neoplasms of any type was
reduced in animals ingesting the cellulose fiber. Compari
son of the mean number of tumors per animal was statisti
cally significant (p < 0.025). The most striking difference,
however, was seen with respect to colonic tumors. Only
30% of the animals ingesting the added highly purified
microcrystalline cellulose diet had grossly detectable co
Ionic neoplasms, compared to 70% of the animals not
eating fiber. Furthermore, the mean number of colonic
neoplasms detected per rat was statistically reduced (p <
0.02) in the animals ingesting the cellulose-containing diet.
As shown small intestinal and ear tumor numbers were
similar between the 2 groups.
treated rats survived to the time of sacrifice. Among the
20% dying before sacrifice, presumptive causes of death
included squamous cell carcinoma of the ear canal, present
in 30% of all carcinogen-injected
animals,
and small intes
tinal or cobonic tumors. Intestinal tumors in these animals
were usuallyassociatedwith complications,includingin
tussusception, obstruction, and hemorrhage as well as
peritoneal, nodal, hepatic, and pulmonary metastases.
Among all 40 carcinogen-injected rats, 34 colonic neo
plasms were detected. Most of these cobonic tumors were
found in the distal colon (76.5%), were sessile plaques or
polypoid, ranged in diameter from 1 to 22 mm (32.4% were
<5 mm, 44.1% were 5 to 10 mm, and 23.5% were >10 mm),
and could be classified as polypoid neoplasms or adenocar
cinomas (23, 24). These findings were essentially similar to
those previously reported for 1,2-dimethylhydrazine-treated
rats (6, 17, 23). Although the relative proportions of small
intestinal tumors are greater in this experimental model
compared to the proportions reported at small and large
intestinal sites in man, the distribution, relative size, and
histopathobogy of cobonic tumors are remarkably similar to
those of human cobonic neoplasia (6, 16, 23).
Tumor Distribution,Size, and Histopathobogy.Results
are shown in Table 5. Besides a greater total number of
cobonic tumors, rats ingesting the fiber-free diet had more
tumors in both proximal and distal colon than did cellulose
ingesting animals. Proportionately, there appeared to be a
shift in tumor distribution from proximal to more distal
colon in the cellulose group. Whereas 26.8% of cobonic
tumors were located in the proximal colon of the fiber-free
group, less than one-half or only 12.5% were found in rats
Tumor Frequency.Table 4 showsthe numberand per
centage of tumor-bearing animals in both groups of carcin
Table 5
Distribution, size, and histopathology ofrat colon
siteMean
distributionHistologyb.
tumorsTotal
Proxl
size of colon tumorsa
(mm)Size
mm
maDistald<5
no. of
masAlltumorsNo.
colonColonic
%tumors
%Fiber-free267
%No.
Proximal
DistalNo.
26.819
73.28.3 ±1.2e 12.5 ±2.9 6.8 ±1.08
61.5group
=(7)!20)Fibergroup(n
(n
62.5=
20)
81
12.57
(87.5)7.5
±2.8
20.0
a Greatest diameter. Only 1 proximal cobonic tumor was detected
b Histological classification of Ward et a!. (23, 24). See text.
C Cecum and ascending colon.
d Descending colon and rectum.
e Mean ±S.E.
I Numbers in parentheses,
mucinous-type
adenocarcinomas.
5-10 mm>10
mmPolypoid
neo
carcino
plasmsAdeno
5.7 ±2.53
% No. %No.
30.8 12 46.26
%No.
23.010
%No.
38.516
37.5
25.03
37.55
3 37.52
(2)
in fiber diet group.
Table6
injectionFiber-free the initial dimethyihydrazine
Tumorappearancefollowing
groupTimed'Animals
diet
diet groupFiber
Animals
colon(wk)mors with tu-
Total tu-
no.21-24213b
mors
±25-281
0.4229-323/3/3
0.2833-36
37-40
41-442/4
5b
(5)C
1 .66 ±058d1/3b
1
3
(6)
(9)
1 .00 ±0.511
1 .00 ±0.292/3
2 (11)
10 (21)
5 (26)
in
@
parentheses,
accumulated
of accumulated
tumors/rat
Mean
morstumor
(2/3)@'
(1/3)@' 2b (2)@'0.66
/3 (2/6)
2 (4)0.66
(4/9) 2 (6)0.66
(4/12) 0 (6)
±
±
±0.23
0.92 ±0.24
0.43 ±0.18e
1/4 (5/16)
1 (7)
1.23 ±0.31
1.30 ±0.270/3 1/4 (6/20) 1 (8)0.500.40 ±0.15@@
a Time interval following the initial injection
b Data from each sacrifice period.
C Numbers
Total tu
mor no.mors
(3/6)
(6/9)
(8/13)
4/4 (12/17)
2/3 (14/20)
sacrifice period.
d Mean number
with tu-
Meancolon tu
of dimethylhydrazine
numbers
of
colon
(at age 29 to 52 weeks).
tumors
up
to
and
including
the
±S.E.
e (t testversusfiber-freecontrolgroup)< 0.05.
fp (t test versus fiber-free
control
group)
< 0.02.
SEPTEMBER1978
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2915
H. J. Freeman et a!.
eating cellulose. Small intestinal tumors were detected only
in the duodenum of both groups.
The size of colonic tumors varied considerably in both
groups. Although they tended to be smaller in the cellulose
group, the difference was not statistically significant. Tu
mors found in the proximal colon were larger than were
tumors in the distal colon regardless of the diet ingested (p
< 0.05).
Among detectable cobonic tumors, 38.2% were classified
as polypoid neoplasms and 61 .8% were classified as inva
sive or metastatic adenocarcinomas. The percentages
of tumors classified as polypoid neoplasms or adenocarci
nomas were remarkably similar between the 2 groups.
Similarly, the mucinous type of adenocarcinoma included
26.9% of detected tumors in the fiber-free group and 25.0%
inthe cellulose
group.Finally,
no siteof predilection
for
distant metastases was apparent between the 2 groups.
Two animals in each group had hepatic metastases. In
addition, one of these rats had a pulmonary metastasis.
ColonicTumorAppearance.Animalswithtumorsaswell
as total tumors within the 2 groups are shown in Table 6. In
general, cellulose-fed animals were less often involved with
colonic tumors at each sacrifice period than was the fiber
free group. In addition, reduced numbers of cobonic tumors
were detected in the cellulose group at each time interval
(except for 25 to 28 weeks). In considering the total accu
mulated cobonic tumor-bearing rats as well as total accu
mulated cobonic tumors to the end of each time period,
numbers were always less in the cellulose-fed group. How
ever, the difference did not become statistically significant
until the final 8 weeks of the study. During these last 2
periods, the differences were most evident. In the fiber-free
group 6 of 7 animals had 15 tumors detected, while in the
cellulose group 2 of 8 rats had only 2 colonic tumors.
cobonic tumors appeared to be similar in size and histopa
thology regardless of whether or not cellulose fiber was
ingested.
Our findings related to tumor incidence resulting from a
highly purified cellulose fiber agree with an earlier report
(27) that examined the effect of a nonpurified fiber-contain
ing substance, wheat bran, in Sprague-Dawley rats. As
acknowledged by the authors, however, the beneficial ef
fects may not have been due only to the fiber portion of
wheat bran. Furthermore, the 20% bran level was achieved
only at the expense of some nonfiber components (sucrose,
casein) in the bran-containing diets. Because both fiber and
nonfiber components may be important potential variables,
we used a single highly purified fiber component with
chemically defined diets of essentially equivalent nutrient
content.
in another study (25) high levels of cellulose bulk did not
appear to reduce the numbers of colonic tumors in Fischer
rats following azoxymethane exposure. Furthermore, large
amounts of cellulose bulk were shown significantly to alter
the food intake of carcinogen-treated animals in their study.
Therefore, the different groups of animals may not have
been comparable.
In this study
a very low level of fiber
administration permitted comparison of 2 apparently similar
groups, at least as judged by food intake during the I -week
metabolic balance and weight gain measured during the
course of the study. Rats appear to increase their intake
with fiber dilution of the diet (25). Similar food intake for
both groups in this study suggests that the level of fiber
(4.5% by weight) did not significantly influence the relative
amounts eaten. Comparison of nutritionally equivalent
groups of animals undergoing carcinogenesis in both of
these former studies (25, 27) might have been important
since caloric restriction per se is thought to inhibit the
formation of many types of tumors, decrease the incidence
of neoplasms, and delay the time at which tumors appear
DISCUSSION
The results of this double-blind study strongly indicate
that dietary cellulose fiber is protective against the devel
opment of cobonic neoplasia in an experimental animal
model. If these findings could be extrapolated to humans,
the hypothesis (2) that fiber deficiency predisposes to
human cobonic neoplasia appears to be well supported. The
observed effects may be directly related to bulk or a specific
physical or chemical property of the dietary fiber compo
nent, cellulose. However, since no other purified fiber
components were examined in this study, it would be
premature to suggest that this beneficial effect could only
have been seen exclusively with cellulose. Similar findings
might have occurred with other fiber components.
The following points summarize the important observa
tions made in the present study: (a) fewer cellulose-ingest
ing animals developed colonic neoplasia; (b) fewer num
bers of cobonic tumors occurred in the cellulose group; (C)
no obvious effect at other sites (small intestine, ear) was
evident with the bevel or duration of fiber administered in
this study; (d) the beneficial effect of cellulose fiber on
colonic tumor incidence appeared to be time dependent;
(e) an apparent proximal to distal shift in cobonic tumor
distribution with cellulose injection was observed; and (f)
2916
(1).
In our study the reduction in cobonictumor incidence did
not become statistically significant until late although the
mean number of tumors was always less at every time
interval
inthe cellulose
group following
the injection
pro
tocol. This apparent time-dependent expression of cellu
lose fiber effect on cobonic neoplasia is not surprising and
may explain the discrepancy from the azoxymethane model
where the rats were examined at a single time period (25).
As previously shown the development of tumors in these
models is determined not only by the total carcinogen
dosage and duration of the injection protocol but also by
the time after the injections at which animals are examined
(17, 20, 21).
While beneficial effects of dietary cellulose fiber were
clearly shown in terms of animals involved as well as tumor
number, no significant differences appeared in relation to
tumor size or histopathology in the present study. However,
tumor distribution appeared to be shifted towards the distal
colon. Although the precise mechanism for this apparent
site redistribution within the colon remains obscure, our
findings do suggest that cellulose fiber affects the colon in
a differential fashion. Some change in the luminal physico
chemical environment from proximal to distal colon or
some inherent difference between the cobonic mucosa itself
CANCER RESEARCHVOL. 38
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Dietary Cellulose Fiber and Colonic Neoplasia in Rats
from these 2 sites may be responsible for the observed
differences. For example, relatively greater fecal content in
proximal colon might lead to greater dilution
of fecal
carcinogens in contact with more proximal colonic mucosa.
Cellulose may enhance this effect (13). Alternatively, since
fiber may shorten colonic transit time (9, 19), delivery of
luminal content (and perhaps luminably active carcinogens
or their metabolites) to the distal colon may be proportion
ately increased, exerting an even greater effect in that
region, or the quantity of cellulose [which is thought to en
hance fecal carcinogen elimination by adsorption to fiber
(13)J may be proportionately reduced in quantity in distal
colon,directly,
by greaterdegradationof celluloseby
bacterial enzymesin proximal colon or, indirectly, by redis
tribution of cobonic microflora within the colon. Finally, the
susceptibility of proximal and distal colonic mucosa to
neoplastic change mayconceivably be different since inher
ent morphological (12, 18)and functional (4)differences do
occur betweenthe 2 regions. While this study has illustrated
that cellulose dietary fiber is 1 preventive factor in experi
mental colonic neoplasia, further studies are needed to
elucidate the underlying molecular mechanisms.
ACKNOWLEDGMENTS
wearegrateful
toTonyCanizales
forhisassistance
inthecareofthe
animals as well as Ruth Miller and Emma Garcia for typing the manuscript.
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Downloaded from cancerres.aacrjournals.org on June 17, 2017. © 1978 American Association for Cancer Research.
2917
A Double-Blind Study on the Effect of Purified Cellulose Dietary
Fiber on 1,2-Dimethylhydrazine-induced Rat Colonic Neoplasia
Hugh J. Freeman, Gene A. Spiller and Young S. Kim
Cancer Res 1978;38:2912-2917.
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