Effect of dietary benzylselenocyanate on azoxymethane‐induced colon carcinogenesis in Male F344 rats

The effect of dietary benzylselenocyanate (BSCJ and its analogue, benzylthiocyanate (BTC), and sodium selenite during the initiation and postinitiation phases of azoxymethane (AOM)‐induced intestinal carcinogenesis was studied in male F344 rats. Animals intended for initiation study were fed the high‐fat (23.5% corn oil) diets containing 25, 50, and 100 ppm BSC (10, 20, and 40 ppm selenium, respectively) and 100 ppm BTC and 4 ppm selenium (as sodium selenite in drinking water); those intended for postinitiation study were fed the high‐fat control diet. Two weeks later, all animals were injected subcutaneously with AOM (15 mg/kg body wt) once weekly for two weeks. Three days after the last AOM injection, animals in the initiation and postinitiation studies were transferred respectively to the high‐fat diet and high‐fat diets containing BSC and BTC and sodium selenite in drinking water. This regimen was continued until 36 weeks post‐AOM injection. BSC inhibited the small intestinal and colon adenocarcinoma incidence and multiplicity of colon adenocarcinomas when fed during the postinitiation phase. Sodium selenite inhibited the incidence and multiplicity of colon adenocarcinomas only during the postinitiation phase. BTC had no inhibitory effect when fed during the initiation and postinitiation phases. The colonic mucosal ornithine decarboxylase activity was significantly inhibited by the administration of all three compounds, BSC (78%), BTC (62%), and sodium selenite (44%). It is concluded that the BSC has an inhibitory effect on the intestinal carcinogenesis in animals fed the high‐fat diet.     

Effect of dietary Laminaria angustata (brown seaweed) on azoxymethane-induced intestinal carcinogenesis in male F344 rats

The effect of dietary Laminaria angustata (brown seaweed) on azoxymethane (AOM)-induced intestinal carcinogenesis was studied in male F344 rats. Five-week old rats were fed semipurified diets containing 0 and 10% seaweed. When the rats were 7 weeks old, all except the vehicle-treated groups received weekly subcutaneous injections of AOM in normal saline for two weeks (20 mg/kg body wt/week). All animals were fed the experimental diets until the termination of the experiment, which was 28 weeks after the last AOM injection. The incidence (percent of animals with tumors) and multiplicity (tumors/animal) of small intestinal tumors did not differ significantly between the control and seaweed groups. The incidence and multiplicity of colon adenomas along with the size of colon tumors were increased in rats fed the seaweed diet compared with those fed the control diet. Dietary seaweed had no major effect on the concentration of fecal bile acids; however, the concentration of fecal cholesterol and total neutral sterols was decreased in the seaweed group. These results suggest that dietary seaweed increases the risk for colon tumors.     

Extract of Kurosu, a vinegar from unpolished rice, inhibits azoxymethane-induced colon carcinogenesis in male F344 rats

The modifying effects of administering an ethyl acetate extract of Kurosu (EK), a vinegar made from unpolished rice, in drinking water on the development of azoxymethane (AOM)-induced colon carcinogenesis were investigated in male F344 rats. Animals were given 2 weekly subcutaneous injections of AOM (20 mg/kg body weight). They also received drinking water containing 0%, 0.05%, or 0.1% EK for 35 wk, starting 1 wk after the last dosing of AOM. EK administration significantly inhibited the incidence and multiplicity of colon adenocarcinoma (P < 0.05), compared with those in the AOM alone group. These findings suggest that EK may be effective for inhibiting colon carcinogenesis.     

Effects of nobiletin on PhIP-induced prostate and colon carcinogenesis in F344 rats

The current study was designed to investigate the effects of nobiletin (5,6,7,8,3',4'-hexamethoxy flavone) on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced prostate and colon carcinogenesis. PhIP was administered to 6-wk-old F344 male rats intragastrically (100 mg/kg) twice a wk for 10 wk. The animals were given 0.05% nobiletin or the basal diet for 50 wk. At the end of the experiment, serum testosterone, estrogen, and leptin did not differ between the 2 groups. The body weights of nobiletin-treated rats were significantly higher than controls (P<0.05), and feeding of nobiletin significantly reduced the relative prostate (P<0.05) and testes (P<0.05) weights as well as the Ki67 labeling index in the normal epithelium in the ventral prostate (P<0.01). The incidence and multiplicity of adenocarcinomas in nobiletin-treated ventral prostate were 50% and 36%, respectively, of controls, but the differences were not statistically significant. However, nobiletin did significantly reduce the total number of colonic aberrant crypt foci (ACF) compared to the control value (P<0.05). Nobiletin, therefore, may have potential for chemoprevention of early changes associated with carcinogenesis in both the prostate and colon.     

Quercetin, but not its glycosidated conjugate rutin, inhibits azoxymethane-induced colorectal carcinogenesis in F344 rats

The effect of the flavonoid quercetin and its conjugate rutin was investigated on (biomarkers of) colorectal cancer (CRC). Male F344 rats (n = 42/group) were fed 0, 0.1, 1, or 10 g quercetin/kg diet or 40 g rutin/kg diet. Two wk after initial administration of experimental diets, rats were given 2 weekly subcutaneous injections with 15 mg/kg body wt azoxymethane (AOM). At wk 38 post-AOM, quercetin dose dependently (P < 0.05) decreased the tumor incidence, multiplicity, and size, whereas tumor incidences were comparable in control (50%) and rutin (45%) groups. The number of aberrant crypt foci (ACF) in unsectioned colons at wk 8 did not correlate with the tumor incidence at wk 38. Moreover, at wk 8 post-AOM, the number and multiplicity of ACF with or without accumulation of beta-catenin were not affected by the 10 g quercetin/kg diet. In contrast, another class of CRC-biomarkers, beta-catenin accumulated crypts, contained less beta-catenin than in controls (P < 0.05). After enzymatic deconjugation, the plasma concentration of 3'-O-methyl-quercetin and quercetin at wk 8 was inversely correlated with the tumor incidence at wk 38 (r = -0.95, P 相似文献   

Green tea, phytic acid, and inositol in combination reduced the incidence of azoxymethane-induced colon tumors in Fisher 344 male rats

Experimental as well as epidemiologic studies in human populations provide evidence that consumption of phytochemicals reduces the incidence of degenerative diseases. Green tea (GT) catechins are known for their antioxidative potential. Phytic acid (PA) also acts as a natural antioxidant and may have numerous health benefits. This experiment was designed to investigate the inhibitory effects of combinations of 1% and 2% GT, PA, and inositol (I) in reducing the incidence of azoxymethane-induced colon tumors in Fisher 344 male rats. After an acclimatization period of 1 week, nine groups of rats (15 rats per group) were initially assigned to consume AIN 93 G diet and later AIN 93 M diet after 20 weeks of age. Treatments were given in drinking water. All rats received azoxymethane injections (16 mg/kg of body weight) subcutaneously at 7 and 8 weeks of age. Rats were killed at 45 weeks of age by CO(2) euthanasia. Tumor incidence (93.76%) and the number of tumors per tumor-bearing rat ratio (2.25) were significantly (P<.05) higher in the control group compared with treatment groups. Glutathione S-transferase activity was significantly (P<.05) higher in rats fed combinations of 2% GT+PA+I and GT+PA (33.25 ± 1.23 and 29.83 ± 1.10 μmol/mL, respectively) compared with other groups. These findings suggest that the synergistic effect of the 2% level of GT, PA, and I may reduce the incidence of colon tumors and therefore have potential as a chemopreventive agent.     

Effect of dietary calcium on colon carcinogenesis induced by a single injection of 1,2-dimethylhydrazine in rats

The purpose of this study was to determine if high levels of dietary calcium could inhibit the induction of colon tumors in rats injected with a single dose of 1,2-dimethylhydrazine (DMH). Rats were given a single subcutaneous injection of DMH (200 mg/kg body weight) 2 wk before they were fed purified diets containing 5% fat and four different levels of calcium (as calcium gluconate). After 8 mo, the following incidences of colon tumors (total) were seen: 0.2% Ca, 56%; 0.5% Ca [National Academy of Sciences/National Research Council (NAS/NRC) recommended level], 75%; 1.0% Ca, 61%; 2.0% Ca, 41%. Thus, rats fed calcium at levels above or below the NAS/NRC recommendation had lower tumor incidences. The total tumor incidence and the incidence of adenocarcinomas (with or without invasion) were not significantly affected by calcium, but the incidences of benign adenomatous polyps and of distal colon tumors were significantly affected. Autoradiographic examination of [3H]thymidine-treated rats revealed that the level of calcium did not significantly alter the cell kinetic indices in the distal colon. In the proximal colon, however, the 0.2% Ca group had a significantly larger proliferative zone, with significantly more labeled cells present at the bottom of the colon crypt. Mineral analysis of tibias and serum samples revealed that rats fed higher levels of calcium had lower bone Fe and serum Mg contents, but no significant trends were seen for Ca, P, Zn or Cu. Therefore, increasing or decreasing the calcium content above or below the NAS/NRC recommendation (supplemented to low fat diets) during the promotional phase of colon carcinogenesis altered the tumor incidence, but the effect was confined to the distal colon and to benign adenomatous polyps.     

The role of dietary phytosterols in colon carcinogenesis.

Epidemiological and experimental studies have shown that increased intake of plant foods and decreased meat consumption are correlated with a decreased risk for colon cancer. Many components of plant foods are suggested to mitigate colon carcinogenesis, including vitamins, minerals, and dietary fiber. Phytosterols are a common component of plant foods consumed in relatively large quantities by vegetarians, who are at lower risk for colon cancer development than individuals on a Western diet low in phytosterols. In addition, phytosterols have been shown experimentally to inhibit colon cancer development. Dietary cholesterol, although structurally similar to the phytosterols, is correlated etiologically to the incidence of colon cancer, with changes in serum cholesterol levels and fecal bile acid profiles suggested to increase susceptibility to colon tumorigenesis. The objective of this paper is to discuss the effect of dietary phytosterols on cholesterol and bile acid metabolism and how these effects may lead to a decreased risk for colon cancer development.     

The effect of age and dietary restriction on bone strength, calcium and phosphorus contents of male F344 rats

At 6 weeks of age, male Fischer F344 rats were fed a purified, casein based diet either ad libitum or in the amount of 60% of the diet consumed by the rats, fed ad libitum (restricted diet). Femur bone tissues were obtained from the rats at 4 and 13 months of age. The femurs of the animals fed ad libitum were significantly stronger than the femurs of the animals fed a restricted diet both at the age of 4 and 13 months [p0.01]. The body weight and bone weight of the animals fed ad libitum were also higher than that of the animals on the restricted diet. The bone ash weight was significantly lower for food restricted animals [p0.013] when compared to the animals fed ad libitum. The bone phosphorus content was significantly higher in the diet restricted older animals [p0.02] when compared to the diet restricted younger animals. Results indicate that food restriction will delay bone maturation.     

Dietary inulin suppresses azoxymethane-induced aberrant crypt foci and colon tumors at the promotion stage in young Fisher 344 rats

This study was designed to determine the effect of 10% dietary long-chain inulin on the azoxymethane (AOM)-induced colonic preneoplastic aberrant crypt foci (ACF) and small intestinal and colon tumors at the initiation (I), promotion (P) and I + P stages (20 rats per treatment) in Fisher 344 male weanling rats. After an acclimatization period of 1 wk, groups of Fisher 344 male weanling rats were assigned to consume AIN 93G diet (control) or AIN 93G diet containing 10% inulin. All the rats received 16 mg/kg body AOM dissolved in saline subcutaneously at 7 wk of age followed by a second injection at 8 wk of age. An additional group of five rats received only saline and consumed the control diet. The rats received the assigned diets until asphyxiation by CO(2) at 16 wk of age for the ACF experiment and 45 wk for the end-point tumor experiment. Feed intake, weight gain, diarrheal index, cecal weight, cecal pH, ACF and tumors in the colon were determined. Rats fed inulin had diarrhea after 2 wk of feeding and recovered by approximately 4 wk. Cecal weight was greater in rats fed inulin and cecal pH was lower. The inulin group had more than 66% fewer aberrant crypts and 60% fewer ACF compared with the control group. Tumor incidences in the small intestine and colon of rats in the control, I, P and I + P groups were: 78, 31, 0 and 11% and 90, 73, 69 and 50%, respectively. The corresponding values for the distal portion of the colon were 87, 63, 45 and 33%, respectively. Colon tumors per tumor-bearing rat were 4.2, 3.09, 1.36 and 1.2 for the control, I, P and I + P groups, respectively. All groups differed, P < 0.05. The results of this study indicate that dietary long-chain inulin suppresses AOM-induced ACF formation, an early preneoplastic marker of colon tumorigenesis in rats, and colon tumors, particularly at the promotion stage.     

Description of the long-term lipogenic effects of dietary carbohydrates in male Fischer 344 rats

The introduction of high fructose corn syrup as a substitute sweetener for sucrose in the mid-1970s has contributed to a general increase in fructose consumption in the U.S. diet. Although several previous investigations suggested that dietary fructose increases serum triglyceride concentration and body fat, these studies have, in general, evaluated this effect in young rats fed the experimental diets for a relatively short period of the life span of the animals. Moreover, these investigations did not control for the possible effects that increased adiposity due to fructose feeding may have on serum triglyceride concentration. The purpose of the current investigation was to describe the long-term effects of specific dietary carbohydrates on serum lipid concentrations and body composition. To this end, we measured serum triglyceride, total cholesterol and HDL cholesterol concentrations and body composition of rats aged 9, 18 and 26 mo that had free access to or were restricted to 60% of free access intake of one of five diets that varied in carbohydrate source (cornstarch, sucrose, glucose, fructose or equimolar fructose plus glucose) starting at 3 mo of age. Dietary fructose significantly increased serum triglyceride concentration across the life span in rats that had free access to food or were calorie restricted. The source of dietary carbohydrate did not have a significant effect on body composition, total cholesterol or the distribution of the cholesterol fractions. These data suggest that dietary fructose per se and not the interaction between fructose and the energy content of the diet increases serum triglyceride concentration in rats.     

Tissue lycopene concentrations and isomer patterns are affected by androgen status and dietary lycopene concentration in male F344 rats

Diets rich in lycopene from tomato products as well as greater concentrations of blood lycopene have been associated with a decreased risk for prostate cancer in epidemiologic studies. However, little is known about factors modulating lycopene absorption, metabolism and tissue distribution in humans and animal models of prostate cancer. A 2 x 4 factorial design was used to measure the effects of androgen status (castrated vs. intact), dietary lycopene concentration (0.00-5.00 g/kg lycopene) and their interaction on tissue lycopene accumulation and isomer patterns in male F344 rats. Male F344 rats ( 14 wk old; 44 castrated, 44 intact) were randomly assigned to one of four diets containing total lycopene concentrations of 0.00, 0.05, 0.50 or 5.00 g/kg as beadlets and fed for 8 wk. Tissue total lycopene and cis/trans lycopene profiles were determined by HPLC. Tissue and serum lycopene concentrations increased significantly (P < 0.01) as dietary lycopene levels increased between 0.00 and 0.50 g/kg. No further increases in serum or tissue concentrations were seen in rats fed dietary lycopene between 0.50 and 5.00 g/kg. As dietary lycopene increased, so did the percentage of cis lycopene in the liver (P < 0.05), due primarily to an increase in the 5-cis isomer. Castrated rats accumulated twice (P < 0.01) the liver lycopene as compared to intact controls, with no effect of castration on serum lycopene or adrenal, kidney, adipose, or lung tissue concentration. Livers from castrated rats had a greater proportion of cis-lycopene than those of intact rats (P < 0.05). A significant interaction between dietary lycopene concentration and androgen status was seen for liver lycopene concentration (P < 0.01). We conclude that serum and tissue lycopene reaches a plateau between 0.05 and 0.50 g/kg dietary lycopene, the tissue cis/trans lycopene ratio increases with greater dietary lycopene and androgens modulate hepatic lycopene metabolism.     

Effect of dietary soybean and licorice on the male F344 rat: an integrated study of some parameters relevant to cancer chemoprevention.

The individual and combined effects of dietary toasted soybean meal (3.13-25%) and dietary licorice root extract (0.38-3.0%) on selected liver and intestinal enzyme levels and on clinical chemistry and histopathological parameters were evaluated on male F344 rats. All parameters were measured one and three months after the 50-day-old rats were started on the diets. By use of newly developed high-performance liquid chromatography-based analytic methods, measurable levels of daidzein (2.67 micrograms/ml) and glycyrrhetinic acid (7.87 micrograms/ml) were detected in the sera of rats on the 25% soybean and 3% licorice diets, respectively. Histopathological evaluations of organs and tissues yielded only nonsignificant strain-related changes. At all dosages, there were no significant soybean- or licorice-related anatomic lesions or hematologic changes. In the clinical biochemistry profile, soybean meal caused moderate but significant dose-dependent decreases in serum cholesterol and increases in alkaline phosphatase, blood urea nitrogen, and phosphorus, which remained within the normal range. Liver glutathione transferase, catalase, and protein kinase C showed significant inductions (up to 50%) in response to increasing doses of soybean meal and licorice extract, with evidence for only marginal interaction between the two additives. Their effects on the intestinal mucosa were not significant. Ornithine decarboxylase levels, an indicator of promotional activity, were unchanged or repressed by the additives. The favorable effects of up to 25% toasted soybean meal and 3% licorice root extract on the levels of the four enzymes, without unfavorable changes in clinical parameters, might account in part for the chemopreventive activities of these additives. These effects would be in addition to direct inhibitory effects of known components in these additives on these or other enzymes or modulation of hormone activity that is not evaluated in this study.     

Effect of dietary fiber on colonic cell proliferation and its relationship to colon carcinogenesis

The addition of specific fiber supplements to semipurified diets has been shown to stimulate large bowel cell proliferation in laboratory rodents. Relatively insoluble fibers such as cellulose, which is poorly fermented, the more-soluble oat bran, and inert bulking agents such as kaolin produce little or no effect on cell growth. On the other hand, wheat bran, pectin, guar gum, and degraded carageenan all stimulate large bowel cell proliferation, the greatest growth response tending to occur in the cecum or proximal colon. The proximal large bowel is also the major site for the intestinal fermentation of dietary fiber and any other nonabsorbed carbohydrates. The fermentation of fiber by colonic microorganisms results in the production of short-chain fatty acids and a lower pH of large bowel contents, metabolic events known to be associated with increased epithelial cell growth. In general, factors that stimulate cell growth also enhance tumor development, a concept that holds true in the colon even for dietary fibers such as pectin and guar gum. Wheat bran can also stimulate colon carcinogenesis when fed only during carcinogen exposure. Oat bran and corn bran may stimulate colon carcinogenesis by increasing fecal bile acid excretion, a feature of many soluble fibers, while the acidification of large bowel contents is associated with an increased frequency of chemically induced colonic cancers. A greater understanding of colonic metabolism and cell physiology is needed to define fully the mechanisms by which dietary fibers modify colon cancer development.     

Dietary inulin suppresses azoxymethane-induced preneoplastic aberrant crypt foci in mature Fisher 344 rats

Preneoplastic aberrant crypt foci (ACF) are generally accepted as reliable markers for colon carcinogenesis in animal models. Rat model ACF studies, however, use younger rats, and there are no published reports on the suitability of adult rats for ACF studies. In this study, inulin, a known suppressor of azoxymethane (AOM)-induced ACF, was tested for its ability to suppress ACF formation in mature rats. After a 2-wk acclimation period, 12-mo-old Fisher 344 retired male breeders received two subcutaneous injections of AOM dissolved in saline at weekly intervals. In experiment 1, six groups received 0, 4, 8, 10, 12 and 16 mg AOM/kg body at each injection and were fed AIN-93M diet. In experiment 2, four groups of rats were fed 10 mg AOM/kg body at each injection based on the results of experiment 1, and were fed 0, 2.5, 5 and 10 g long-chain inulin diets/100 g. All the rats were killed after 11-wk feeding periods. In experiment 1, there was a significant (P < 0.05) AOM dose response on ACF formation. Rats fed >10 mg of AOM had greater (P < 0.05) mortality. In experiment 2, there was a significant increase in cecal weight and a decrease in cecal pH from 7.17 in the control group to 6.87, 6.61 and 5.76 in the groups fed inulin at 2.5, 5.0 and 10 g/100 g, respectively. Long-chain inulin dose-dependently reduced ACF incidence in the colon (P < 0.01). Compared with rats fed the control diet, the percentage reductions of ACF in rats fed 2.5, 5.0 and 10 g inulin diets/100 g were 25, 51, and 65, respectively. The results of this study indicate that mature rats can be used as models in ACF studies, and dietary long-chain inulin dose-dependently suppresses AOM-induced ACF formation in Fisher 344 mature male rats.     

Testosterone and food restriction modulate hepatic lycopene isomer concentrations in male F344 rats

We previously demonstrated that the castration of male rats profoundly increases hepatic lycopene compared with intact controls. Here we further characterized the role of testosterone in modulating hepatic lycopene accumulation and isomer patterns in male rats. Furthermore, because castration significantly decreases ad libitum food consumption, we investigated the influence of food restriction on lycopene metabolism. Forty male F344 rats 8 wk of age were randomly assigned to one of four treatments (n = 10/group): 1) intact, free access to food, 2) castration, free access to food, 3) castration plus testosterone implants, free access to food and 4) intact, 20% food restricted. All rats were fed an AIN-based diet with 0.25 g lycopene (as 10% water-soluble beadlets)/kg diet for 3 wk. Serum testosterone was 5.31 +/- 1.46 nmol/L in intact controls allowed free access to food, reduced in castrated animals (0.52 +/- 0.10, P < 0.0001 versus controls) and intact, food-restricted rats (1.53 +/- 0.49 nmol/L, P < 0.0001 versus controls) and greater (17.23 +/- 3.09 nmol/L) in castrated rats administered testosterone (P < 0.0001 versus controls). Castrated rats accumulated approximately twice as much liver lycopene (74.5 +/- 8.5 nmol/g; P < 0.01 versus controls) as intact rats allowed free access to food (39.5 +/- 5.0) despite 13% lower dietary lycopene intake (P < 0.001; 3.38 +/- 0.07 versus 3.95 +/- 0.06 mg lycopene/d). Testosterone replacement in castrated rats returned liver lycopene concentrations (32.5 +/- 5.5 nmol lycopene/g with 3.76 +/- 0.05 mg dietary lycopene/d) to those observed in intact rats. Food restriction resulted in a 20% decrease in lycopene intake but significantly increased liver lycopene by 68% (66.3 +/- 7.9 nmol lycopene/g with 3.38 +/- 0.00 mg lycopene/d) compared with controls and castrated rats administered testosterone. These results suggest that androgen depletion and 20% food restriction increase hepatic lycopene accumulation. We hypothesize an endocrine and dietary interaction, where higher androgen concentrations and greater energy intake may stimulate lycopene metabolism and degradation.     

Age and dietary form of vitamin K affect menaquinone-4 concentrations in male Fischer 344 rats

Phylloquinone, the primary dietary form of vitamin K, is converted to menaquinone-4 (MK-4) in certain tissues. MK-4 may have tissue-specific roles independent of those traditionally identified with vitamin K. Fischer 344 male rats of different ages (2, 12, and 24 mo, n = 20 per age group) were used to compare the conversion of phylloquinone to MK-4 with an equivalent dose of another dietary form of vitamin K, 2',3'-dihydrophylloquinone. Rats were age- and diet-group pair-fed phylloquinone (198 +/- 9.0 microg/kg diet) or dihydrophylloquinone (172 +/- 13.0 microg/kg diet) for 28 d. MK-4 was the primary form of vitamin K in serum, spleen, kidney, testes, bone marrow, and brain myelin fractions, regardless of age group. MK-4 concentrations were significantly lower in kidney, heart, testes, cortex (myelin), and striatum (myelin) in the dihydrophylloquinone diet group compared with the phylloquinone diet group (P < 0.05). The MK-4 concentrations in 2-mo-old rats were lower in liver, spleen, kidney, heart, and cortex (myelin) but higher in testes compared with 24-mo-old rats (P < 0.05). However, there were no age-specific differences in MK-4 concentrations among the rats fed the 2 diets. These data suggest that dihydrophylloquinone, which differs from phylloquinone in its side phytyl chain, is absorbed but its intake results in less MK-4 in certain tissues. Dihydrophylloquinone may be used in models for the study of tissue-specific vitamin K deficiency.     

Effect of dietary soybean and licorice on the male F344 rat: An integrated study of some parameters relevant to cancer chemoprevention

The individual and combined effects of dietary toasted soybean meal (3.13–25%) and dietary licorice root extract (0.38–3.0%) on selected liver and intestinal enzyme levels and on clinical chemistry and histopathological parameters were evaluated on male F344 rats. All parameters were measured one and three months after the 50‐day‐old rats were started on the diets. By use of newly developed high‐performance liquid chromatography‐based analytic methods, measurable levels of daidzein (2.67 μg/ml) and glycyrrhetinic acid (7.87 μg/ml) were detected in the sera of rats on the 25% soybean and 3% licorice diets, respectively. Histopathological evaluations of organs and tissues yielded only nonsignificant strain‐related changes. At all dosages, there were no significant soybean‐ or licorice‐related anatomic lesions or hematologic changes. In the clinical biochemistry profile, soybean meal caused moderate but significant dose‐dependent decreases in serum cholesterol and increases in alkaline phosphatase, blood urea nitrogen, and phosphorus, which remained within the normal range. Liver glutathione transferase, catalase, and protein kinase C showed significant inductions (up to 50%) in response to increasing doses of soybean meal and licorice extract, with evidence for only marginal interaction between the two additives. Their effects on the intestinal mucosa were not significant. Ornithine decarboxylase levels, an indicator of promotional activity, were unchanged or repressed by the additives.

The favorable effects of up to 25% toasted soybean meal and 3% licorice root extract on the levels of the four enzymes, without unfavorable changes in clinical parameters, might account in part for the chemopreventive activities of these additives. These effects would be in addition to direct inhibitory effects of known components in these additives on these or other enzymes or modulation of hormone activity that is not evaluated in this study.     

Influence of dietary cis- and trans-fat on 1,2-dimethylhydrazine-induced colon tumors and fecal steroid excretion in Fischer 344 rats

To investigate the effects of the difference in the geometry of dietary fatty acids on colon tumorigenesis, male rats were fed semipurified diets containing either partially hydrogenated corn oil (trans-monoene fat) or olive oil (cis-monoene fat) at the 10% level and received a single oral dosage of 1,2-dimethylhydrazine (DMH). The difference in the fatty acid composition of dietary fats was confined essentially to the geometrical isomerism of octadecenoate, and the linoleic acid content was made equivalent (2% of total energy). After about 15 mo of feeding, colon tumor incidence in DMH treated rats was nearly the same in both fat groups. Fecal neutral steroid excretion was higher, while the transformation of cholesterol to coprostanol was lower in rats given the trans-fat. There were no marked differences in the excretion and composition of fecal bile acids between two fat groups. Serum cholesterol and tocopherol levels of rats given trans-fat diets tended to be low. The results suggested that the trans-monoene behaves much like the cis-monoene in the incidence of DMH-induced colon tumors, although there were characteristic differences in metabolic events in the intestine.     

Effect of complex polyphenols on colon carcinogenesis

Summary Background: Complex polyphenols and tannins from wine (WCPT) are being considered increasingly as potential cancer chemopreventive agents, since epidemiological studies suggest that populations consuming a high amount of polyphenols in the diet may have a lower incidence of some types of cancer. Aim of the study: We studied the effect of WCPT on a series of parameters related to colon carcinogenesis in rats. Methods: WCPT were administered to F344 rats at a dose of 14 or 57 mg/kg/d, mixed with the diet. The higher dose is about ten times the exposure to polyphenols of a moderate drinker of red wine. In rats treated with WCPT, we measured fecal bile acids and long chain fatty acids, colon mucosa cell proliferation, apoptosis and, after administration of colon carcinogens, the number and size of aberrant crypt foci (ACF) and nuclear aberrations. Results: Colon mucosa proliferation was not varied by chronic administration (90 d) of WCPT (14 or 57 mg/kg/d). The highest dose of WCPT decreased the number of cells in the colon crypts, but did not increase apoptosis. WCPT (57 mg/kg) administered before or after the administration of azoxymethane (AOM) did not vary the number or multiplicity of ACF in the colon. The number of nuclear aberrations (NA) in colon mucosa was studied after administration of 1,2-dimethylhydrazine (DMH) and 2-amino-3-methylimidazo (4,5-f)quinoline (IQ), colon-specific carcinogens which require metabolic activation. The effect of DMH and IQ was not varied by pre-feeding WCPT (57 mg/kg) for 10 d. Similarly, the levels of total, secondary bile acids and long chain fatty acids did not varied significantly in animals fed WCPT for 90 d. Conclusions: WCPT administration does not influence parameters related to colon carcinogenesis in the rat. Received: 18 January 1999, Accepted: 18 May 1999