Biomedical subjects

F Bianchini

Publications and source records attributed to F Bianchini.

At least 37 records · Page 2Linked to original sources

PubMed1998

Urinary excretion of 5-(hydroxymethyl) uracil in healthy volunteers: effect of active and passive tobacco smoke.

The urinary excretion of 5-(hydroxymethyl)uracil (5-HMUra), one of the major oxidative modifications of thymine, was investigated in 134 healthy volunteers living in North Italy. Overnight urine was collected, and a questionnaire was completed on smoking habits and exposure to environmental tobacco smoke (ETS). 5-HMUra was analyzed by GC/MS, following urine purification by HPLC. 5-HMUra excretion showed an approximately normal distribution, ranging from 0.08 to 0.84 (mean 0.44) nmoles/kg/8 hr and from 3.2 to 18.7 (mean 8.5) nmoles/mmoles creatinine. 5-HMUra excretion was significantly higher in women than in men and in smokers than in non-smokers when results were expressed as the ratio to creatinine. Slightly higher levels of 5-HMUra excretion, expressed as nmoles/mmoles creatinine, were also found in subjects highly exposed to ETS, monitored either as the number of hours of exposure or as the number of smokers in the workplace and at home. Our results show that the urinary excretion of 5-HMUra is higher than that of other oxidized nucleobases, including 8-oxo-7,8-dihydroguanine, and can be slightly modified by environmental factors such as tobacco smoke. These findings suggest that measurement of urinary excretion of 5-HMUra could be useful as a biomarker of oxidative DNA damage and repair, though further research is needed to support these data.

Adult↗

PubMed1996

5-Hydroxymethyluracil excretion, plasma TBARS and plasma antioxidant vitamins in adriamycin-treated patients.

The thymine oxidative lesion-5-hydroxymethyluracil (HMUra)-was measured in urine collected from cancer patients. These patients all received chemotherapy using Adriamycin. Adriamycin (ADR) intercalates DNA coils and interferes with normal cell metabolism through diverse biochemical mechanisms that may explain its different actions. The anticancer action of ADR could derive from its interaction with topoisomerase II, resulting in DNA nicking followed by DNA fragmentation and apoptosis. Side effects of ADR-mainly its cardiotoxicity-may derive from the fact that ADR generates superoxide and hydroxyl radicals in two ways: redox-cycling and a Haber-Weiss type reaction due to Fe-ADR complexes. The oxygen free radicals, particularly .OH, are thought to be produced by ADR directly in genomic material and attack all its components. 5-Hydroxymethyluracil is a thymine lesion provoked by these attacks, and it has been proposed as a marker of DNA alterations. In this article, we report the results of a study involving 14 cancer patients treated with ADR. We found that urine HMUra is significantly increased by the anticancer therapy (HMUra (nmol/24 h): 74.4 9.46 vs. 96.3 8.74; p < .01), this increase reveals a higher risk of mutagenesis. Our study is the first to show an in vivo alteration of DNA by ADR. Results also show that thiobarbituric acid reactants increase significantly, and that the vitamin levels for retinol and alpha-tocopherol, which are antioxidant vitamins, are lower at the end of chemotherapy. We suggest to supplement these patients with vitamins A and E, and selenium to reduce the side effects of ADR.

Adult↗

PubMed1996

Observation and prevention of an artefactual formation of oxidized DNA bases and nucleosides in the GC-EIMS method.

Gas chromatography coupled to electron impact mass spectrometry (GC-EIMS) analysis following hydrolysis of DNA is a widely used assay for the detection of oxidized nucleobases and nucleosides. However, evidence was recently provided for an oxidation of guanine residues of hydrolysed DNA during the silylation prior to GC-EIMS analysis. This reaction accounts for the overestimation of the yield of 8-oxo-7,8-dihydroguanine by GC-EIMS. In the present work, we showed that adenine, cytosine, thymine and thymidine also give rise to oxidized derivatives during the derivatization. This was inferred from the measurement of the amount of 5-formyluracil, 5-hydroxymethyluracil, 5-hydroxycytosine (5-OHCyt), 8-oxo-7,8-dihydroadenine (8-OxoAde) and 5-hydroxymethyl-2'-deoxyuridine (5-HMdUrd) in a series of experiments based on the use of purified bases and nucleosides. Isotopically labelled oxidized bases and 5-HMdUrd were used as internal standards to control the quantitative aspect of the silylation reaction. Support for an artefactual oxidation of hydrolysed DNA was provided by the comparison of the amount of 8-OxoAde and 5-OHCyt detected within native and gamma-irradiated DNA by HPLC-EC and GC-EIMS. To prevent the artefactual formation of oxidized bases during the silylation, an approach based on an HPLC prepurification was developed to remove the precursors of the oxidized bases measured in the DNA sample. The HPLC/GC-EIMS assay was successfully applied to the quantitation of 8-OxoAde and 5-OHCyt in calf thymus DNA. In addition, the detection of the dose-dependent formation of 5-HMdUrd in isolated DNA exposed to ionizing radiation was achieved using the same approach.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1994

Effect of route of administration of environmental methylating agents on 7-methylguanine formation in white blood cells and internal organs: implications for molecular epidemiology.

The measurement of 7-methylguanine (7-meG) in white blood cells (WBC) is a promising biomarker of individual human exposure to environmental methylating agents. To test the validity of using WBC as a surrogate dosimeter for internal tissues, levels of 7-meG were measured in rat WBC, liver and target organs for carcinogenesis 16 h after oral administration of several methylating carcinogens (DMN, DMH, NNK, NMBA). 7-MeG was detected in WBC DNA but levels were far lower than in internal organs. While the ratio between 7-meG formation in target organs and WBC was highly variable depending on the carcinogen administered, the ratio between 7-meG in the liver and WBC was in the same order of magnitude for each carcinogen, ranging from 81 to 143. In addition, levels of 7-meG in the liver and WBC within individual animals were highly correlated (r = 0.94, P < 0.0001). These results confirmed our previous observations with the same carcinogens after intraperitoneal injection. In order to assess if the lower level of 7-meG in WBC was a result of a low metabolism of methylating agents in WBC, microsomes were prepared from control rat lymphocytes and DMN demethylase activity was measured. The total amount of microsomal proteins was extremely low, especially in comparison with hepatic cells, and the enzymatic activity was less than 0.48 nmol HCHO/min/mg protein, while an activity of 1.26 nmol HCHO/min/mg protein was measured in liver microsomes. Taken together, these results suggest that the presence of 7-meG in WBC DNA reflects an exposure to methylating agents; the level of 7-meG in WBC seems predictive of the level of adduct in the liver, possibly because active methylating species are formed in the liver and then transferred into the hepatic circulation, where the WBC are exposed. It is now important to examine this relationship in humans where exposures are generally to lower levels of carcinogens over long time periods.

Administration, Oral↗

PubMed1994

Rectal proliferation and polyp occurrence in patients with familial adenomatous polyposis after sulindac treatment.

BACKGROUND/AIMS: Sulindac, a nonsteroidal anti-inflammatory drug (NSAID), decreases the occurrence of polyps in patients with familial adenomatous polyposis (FAP). The effects of colectomy with ileorectal anastomosis (IRA) and sulindac treatment on rectal mucosa proliferation and polyp occurrence were examined in patients with FAP. METHODS: The number and size of rectal polyps were measured with colonoscopy. The labeling index, the percentage of labeled cells per crypt compartment, was assessed in rectal biopsy specimens with [3H]thymidine incorporation and autoradiography in 6 non-IRA and 14 IRA patients before and after treatment with 200 mg of sulindac/day for 60 days. RESULTS: The IRA patients had a lower labeling index and a decrease in the percentage of labeled cells in the upper compartment of the crypt (P < 0.01) relative to non-IRA subjects. Sulindac did not influence the labeling index and the distribution of labeled cells along the crypt. On the contrary, a dramatic decrease in the size and number of polyps was observed after sulindac treatment (P < 0.001). CONCLUSIONS: The persistence of a abnormal mucosal proliferation after sulindac therapy, in spite of the reduction of polyp number, suggests caution in assuming a lower risk of rectal cancer in patients with FAP.

Adenomatous Polyposis Coli↗

PubMed1994

7-Methyldeoxyguanosine as a marker of exposure to environmental methylating agents.

7-Methyldeoxyguanosine (7-medG) may be a useful marker of human exposure to methylating agents at the individual level. Methods of detection, including 32P-postlabeling, HPLC with electrochemical or fluorescence detection, and immunoassays, are critically summarized. These methods have been applied to the analysis of 7-medG in human samples, resulting from environmental exposure or endogenous processes. Detectable levels of adduct have been demonstrated in several tissues (liver, lung, bronchial, pancreas) and peripheral white blood cells. Studies are in progress to verify the possible use of white blood cells as a surrogate for internal organs.

Alkylating Agents↗

PubMed1994

Comparison of 7-medG formation in white blood cells, liver and target organs in rats treated with methylating carcinogens.

The relationship between 7-methylguanine (7-meG) formation in white blood cells (WBC) and internal organs after treatment with methylating carcinogens has been studied in rats, in order to assess the possible use of WBC as a surrogate for target organs in epidemiological studies. Animals were treated with a single intraperitoneal injection of DMN, DMH or NMBA or with a subcutaneous injection of NNK, at different dose levels, and killed 16 h after treatment. 7-meG, following thermal hydrolysis and immunopurification, was analysed by HPLC with electrochemical detection. Administration of methylating carcinogens resulted in the dose-dependent formation of 7-meG in WBC DNA; the adduct level, however, was markedly lower than in internal organs. The ratio between 7-meG formation in target organ and WBC was a function of the carcinogen administered, varying from 3.6 with NNK to 200 with NMBA. On the other hand, the ratio between 7-meG in the liver and WBC was of the same order of magnitude for each carcinogen, ranging from 35 to 100. These results show that the presence of 7-meG in WBC DNA is indicative of adduct formation in internal organs, particularly in the liver, and suggest that active methylating species may be formed in the liver and then transferred to the WBC where they can methylate DNA.

1,2-Dimethylhydrazine↗

PubMed1993

The growth of preneoplastic lesions by 1,2-dimethylhydrazine in rat colon is inhibited by dietary starch.

The effect of dietary starch and sucrose on colon proliferation and the growth of foci of dysplastic crypts in the colon (FDC) were studied in female Sprague-Dawley rats, treated p.o. with 1,2-dimethylhydrazine (DMH). The animals were fed for 30 and 105 days with high fat (23% w/w corn oil) diets in which carbohydrates were represented by corn starch (starch diet) or sucrose (sucrose diet) (46% w/w). After 105 days of feeding, proliferation was markedly reduced in animals fed the starch diet. The number of FDC was not significantly affected by dietary treatments. However, after 30 and 105 days the percent of small FDC (formed by one-two dysplastic crypts) was higher in the animals fed the starch diet when compared to the sucrose diet. In the cecum of the animals fed the starch diet the percent of butyrate, propionic, isovaleric, and valeric over total short-chain fatty acids (SCFA) was increased, whereas the percent of acetic acid was decreased. Cecal pH was also decreased in the animals fed starch. The results suggest that starch diets have a protective role against DMH-colon carcinogenesis in the rat, mediated by a drop in cecal pH and an increased concentration of some SCFA.

1,2-Dimethylhydrazine↗

PubMed1993

Mitotic activity in colorectal mucosa of healthy subjects in two Italian areas with different dietary habits.

The proliferative activity was evaluated in colorectal biopsies of 39 healthy subjects living in two distinct geographical areas, Trieste in northern and Florence in central Italy. Subjects living in Trieste had a significantly higher mitotic activity compared with subjects living in Florence (mitoses/cells counted x 100 were 0.17 +/- 0.04 in Trieste and 0.089 +/- 0.02 in Florence). The results of a dietary questionnaire also showed that subjects in Trieste consumed significantly fewer starches, fibers, nitrites, and proteins. However, no correlation was evident between the consumption of these nutrients and intestinal proliferation.

Adult↗

PubMed1993

Quantification of 7-methyldeoxyguanosine using immunoaffinity purification and HPLC with electrochemical detection.

7-Methylguanine (7-meG) could be a useful marker of recent past exposure to environmental methylating agents for use in epidemiological studies. A method is described that is appropriate for such an application. 7-meG was released from DNA by thermal hydrolysis under conditions (pH 9, 70 degrees C, 8 h) that preferentially released the base from DNA rather than RNA and, following immunopurification using antibodies specific for this DNA adduct, quantification was achieved either by HPLC with electrochemical detection (ECD) or by ELISA. The detection limits of the two approaches were 0.5 and 2 pmol 7-meG/DNA sample respectively. 7-meG was analysed in DNA samples contaminated with known amounts of RNA to test the possible interference in the analysis by the minor modified nucleoside 7-methylguanine, which is present as a normal component of RNA. 7-meG levels measured in human pancreas and untreated rat liver DNA were between 2 and 7 pmol 7-meG/mumol guanosine and this level could not be explained by RNA contamination. The combination of immunoaffinity purification and HPLC with ECD provides a method that is sensitive and specific for 7-meG and suitable for integration into molecular epidemiological studies.

Animals↗

PubMed1993

Rats fed high starch diets have lower colonic proliferation and fecal bile acids than high sucrose-fed controls.

We studied the effects of sucrose or starch in the diet (460 g/kg diet) on fecal bile acid concentrations in Sprague Dawley rats after 4 wk of feeding. Total bile acid concentration in the feces was significantly lower in the rats fed the starch diet than in those fed the sucrose diet (4.56 +/- 0.47 mg/g dry weight and 8.03 +/- 0.94, respectively, SEM), due to a reduction of deoxycholic, alpha-muricholic and beta-muricholic acids. Fecal and cecal pH values were significantly lower in the rats fed the starch diet compared to those fed the sucrose diet (6.79 +/- 0.08 and 7.15 +/- 0.09 for fecal pH and 7.02 +/- 0.05 and 7.2 +/- 0.04 for cecal pH in the two diet groups, respectively). Colon proliferation was also significantly lower in the starch-fed rats compared to those fed sucrose (labeling index 3.51 +/- 0.6 and 5.69 +/- 0.74, respectively), and the reduction was apparent in the middle and upper compartments of the colon crypts. The mucosal proliferation, expressed as percentage of labeled cells in the upper compartment of the colon crypts, was positively correlated with the concentration of deoxycholic, lithocholic, alpha-muricholic, beta-muricholic, cholic and total bile acids in the feces (per gram wet weight). The results indicate a protective effect of starch versus sucrose diets on colon mucosa.

Administration, Oral↗

PubMed1992

Profile of short-chain fatty acids and rectal proliferation in rats fed sucrose or cornstarch diets.

Rats were fed high fat (231 g/kg diet), low calcium (1.3 g/kg diet), low cellulose (20 g/kg diet) diets in which carbohydrates were represented by sucrose or starch (460 g/kg diet). A subgroup of animals was treated with 1,2-dimethylhydrazine (DMH) twice, 4 and 8 d before the beginning of the dietary treatments. Animals fed the starch diet, compared with those fed the sucrose diet, had higher concentrations of cecal and fecal short-chain fatty acids and a significantly lower acetic acid:butyric acid ratio in the cecal contents at d 105. Ratios were 14.7 +/- 1.7 and 6.8 +/- 0.4 for rats fed the sucrose and starch diets, respectively (P less than 0.01). Cecal pH was significantly lower in animals fed the starch diet for 105 d. At d 105, rectal proliferation was lower in rats fed the starch diet (labeled cells/crypt were 7.89 +/- 0.56 and 3.57 +/- 0.40 for rats fed the sucrose and starch diets, respectively, P less than 0.01); at d 30 the effect of starch on proliferation was evident in controls but not in DMH-treated rats. Rectal proliferation data were negatively correlated with the concentration and percentage of butyric acid and positively correlated with the percentage of acetic acid, the acetic acid:butyric acid ratio and cecal pH. These results suggest that low rectal proliferation in animals fed a high fat, high starch diet might be associated with a lower relative concentration of butyric acid in the cecal contents.

1,2-Dimethylhydrazine↗

PubMed1991

Effect of dietary carbohydrates on the growth of dysplastic crypt foci in the colon of rats treated with 1,2-dimethylhydrazine.

The effect of dietary starch and sucrose on the growth of foci of dysplastic crypts in the colon (FDC) was studied in female Sprague Dawley rats treated twice p.o. with 25 mg/kg of 1,2-dimethylhydrazine (DMH). After DMH administration, the animals were fed high-fat (23% corn oil, w/w)/low-calcium (0.1%, w/w)/low-cellulose (2%, w/w) diets in which carbohydrates were represented by corn starch (starch diet) or sucrose (sucrose diet) (46%, w/w). The animals were fed for either 30 or 105 days with the experimental diets. The number of FDC was not significantly affected by diet. However, after 30 days the percentage of small FDC (formed by 1-2 dysplastic crypts) was higher in the animals fed the starch diet compared to the animals fed the sucrose diet [90.3 +/- 1.1% (SE) and 82.6 +/- 3.1%, respectively; P less than 0.05]. In contrast, foci formed by 3-4 dysplastic crypts were decreased by the starch diet (P less than 0.05). After 105 days of feeding, the starch diet induced a number of dysplastic crypts/focus lower than that induced by the sucrose diet (2.6 +/- 0.1 and 2.9 +/- 0.1, respectively; P less than 0.05). The percentage of small FDC was also higher in the animals fed the starch diet compared to animals fed the sucrose diet (P less than 0.01). After 30 days of feeding, DMH treatment increased colon proliferative activity in both dietary groups (P less than 0.05). But after 105 days of feeding, proliferation was similar in controls and DMH-treated rats and markedly reduced in animals fed the starch diet (mean labeling index values for both controls and DMH-treated rats were 10.4 +/- 0.8 and 4.4 +/- 0.5 in the sucrose and starch diets, respectively; P less than 0.001). The overall results suggest that starch in high-fat/low-calcium/low-cellulose diets has a protective role against DMH-colon carcinogensis in the rat.

1,2-Dimethylhydrazine↗

PubMed1991

Mucosal cell proliferation of the rectal stump in ulcerative colitis patients after ileorectal anastomosis.

The proliferative activity and polyamine levels of the rectal epithelium in unoperated ulcerative colitis patients and in ulcerative colitis patients after total colectomy and ileorectal anastomosis were determined and compared with control subjects. Cell proliferation was evaluated in rectal biopsies by in vitro 3H thymidine incorporation by measuring the labeling index and the position of labeled cells along the crypt; polyamines were determined with a chromatographic method. In ulcerative colitis patients the labeling index was significantly increased, and labeled cells were shifted toward the upper part of the crypt when compared with controls. Ileorectal anastomosis patients showed a normalization of the labeling index and a distribution of labeled cells similar to controls. Polyamine levels were also increased in ulcerative colitis patients; in ileorectal anastomosis patients, the level of polyamines was decreased in respect to unoperated patients and return to normal values except for spermine. Because the increased proliferation and higher polyamine levels are related to increased colon cancer risk, our results confirm that ulcerative colitis is a risk factor for the development of carcinoma. Ileorectal anastomosis may reduce this risk through a normalization of mucosal cell proliferative activity and of some polyamine levels.

Adolescent↗

PubMed1991

Starchy foods and colon proliferation in mice.

The effect of starch contained in different foods on colonic proliferation was studied in C57BL/6N mice after four weeks of feeding with 20% fat diets containing cornstarch, white bread, pasta, and rice; an equicaloric amount of sucrose was used in a control diet. Cell proliferation was evaluated in different subsites of the colon (rectal end, mid colon and cecal end) by colchicine arrest and [3H]thymidine incorporation. The following parameters were analyzed: mitotic index (MI), labeling index (LI), and the distribution of labeled cells along the crypt. Different results were obtained in the different subsites. At the rectal end of the colon, all diets containing starch lowered cell proliferation compared with the sucrose diet. The values for MI in the different diets were 2.56 +/- 0.22, 1.73 +/- 0.30, 1.37 +/- 0.19, 1.61 +/- 0.29, and 1.29 +/- 0.31 for control, cornstarch, white bread, pasta, and rice, respectively. Values are means +/- SE (n = 10). The values for LI showed a similar pattern. In the mid colon, the MI was significantly lowered only by the diet containing rice, whereas the DNA synthetic activity (LI) was lowered by cornstarch, pasta, and rice. Toward the cecal end, we observed a significant reduction in MI with diets containing pasta and rice and in the LI with diets containing pasta. The distribution of the LI along the crypt in the different subsites was not significantly affected by experimental dietary variations. The results suggest that starch from different dietary sources might reduce colon proliferation in the mouse.

Analysis of Variance↗

PubMed1991

Gastric hyperplastic changes and thymidine uptake after partial gastrectomy in rats.

Foveolar hyperplastic changes have been recently considered to be the most distinctive histological findings following partial gastrectomy, and their relationship to bile reflux has been proven. The present study was undertaken in order to determine whether an increase in 3H-thymidine uptake, which is an expression of increased gastric mucosal proliferative activity, might correspond to these hyperplastic changes. Histology and thymidine uptake values were assessed and compared in nineteen rats operated upon either with a Polya gastrectomy (11) or with a Roux-en-Y biliary diversion (8). Thymidine uptake values and the extent of gastric hyperplastic changes were greater in the Polya than in the Roux-en-Y group. Moreover, a significant correlation was found between thymidine uptake values and the extent of hyperplastic changes. Therefore, the relationship between hyperplastic changes and increased mucosal proliferative activity post-gastrectomy would seem to have been proven. Since bile acids have been shown to be able to stimulate cell proliferation in ileal and colonic mucosa, a role for bile reflux in the increased cell proliferation activity in the gastric stump can be hypothesized.

Anastomosis, Roux-en-Y↗

PubMed1990

Effect of dietary lipids on hepatic and intestinal monooxygenases in mice.

The effect of dietary lipids on hepatic and intestinal monooxygenases was studied by feeding C57BL/6N mice (for 2 wks) diets containing 5% and 23.5% (wt/wt) olive oil or corn oil. At the end of the feeding period, we measured arylhydrocarbon hydroxylase (AHH) activity in S9 preparations from liver, small intestine, and colon; and, using the same S9 preparations from the liver, we observed the activation of the following three dietary promutagens: 2-amino-3-methylimidazo(4,5-f)quinoline, 2-amino-3,8-dimethylimidazo(4,5-f) quinoxaline, and 2-amino-6-methyldipyrido(1,2-a:3',2'-d)imidazole. The results showed that high-fat diets increased hepatic AHH activity both in corn oil and olive oil diets compared with the low-fat diets; also, a 5% corn oil diet had significantly higher AHH activity compared with the 5% olive oil diet. AHH activity was, respectively, 48.6 +/- 5.1 and 79.5 +/- 11.4 pmol 3OH-benzo[a]pyrene formed/mg/min in the 5% and 23.5% olive oil diets and 66.1 +/- 5.1 and 83.9 +/- 12.2 in the 5% and 23.5% corn oil diets; values are means +/- SE, n = 16. The results also showed a significant increase in the ability of hepatic S9 fractions from animals on high-fat diets to activate promutagens in the Salmonella/plate test. On the contrary, AHH activity in the small intestine and colon was not affected by the fat content of the diet.

Animals↗

PubMed1989

Proliferative activity in the colon of the mouse and its modulation by dietary starch, fat, and cellulose.

The effect of dietary starch, fat, and cellulose on colonic proliferation was studied in female C57Bl/6J mice after 4 weeks of feeding with diets containing various levels of starch (3, 36, and 57-65%), various levels of fat (corn oil, 5 and 29%) and various levels of cellulose (2 and 10%). Cell proliferation was measured by colchicine arrest and [3H]thymidine incorporation. The following parameters were analyzed: mitotic index, labeling index, and position of labelled cells along the crypt. Increasing starch content from 3 to 36% decreased cell proliferation both in low (5%) and high (29%) fat diets. By estimating simultaneously the effects of starch and fat with a single multiple regression model, we observed a decrease of mitotic index from 3.04 +/- 0.34 to 2.04 +/- 0.43 (means +/- SE) (P less than 0.05) when starch was increased from 3 to 36% regardless of the level of fat. Other proliferation parameters showed a similar pattern. Changes in dietary fat alone did not affect significantly cell proliferation. We also investigated the effect of starch at high levels (57-65%) and its interactions with cellulose. High starch (57-65%) increased the labeling index from 7.70 +/- 0.58 to 9.65 +/- 0.88 (P less than 0.05), when also considering the effect of cellulose in the multiple regression model. Cellulose by itself did not change the labeling index. Varying starch from 36 to 57-65% increased the number of cells/crypt column from 22.20 +/- 0.82 to 25.87 +/- 1.21 (P less than 0.05) and varying cellulose from 2 to 10% increased the number of cells/crypt column from 22.20 +/- 0.82 to 27.25 +/- 0.97 (P less than 0.01). The results indicate that either high or low fat diets, containing 36% starch, have the minimum proliferative effects in the mouse colon. However, diets containing high levels of both starch (57%) and cellulose (10%) may induce an increase in proliferation. These data suggest a potential beneficial effect of starch on colon proliferation.

Animals↗