The interaction of dietary fat and antiestrogen treatment on DMBA‐induced mammary tumors in the rat

This study was designed to determine whether an estrogenic mechanism is in volved in dietary fat‐modulated tumor development and growth. Female Sprague‐Dawley rats were placed on a semipurified low‐fat (2% fat), high‐saturated fat (20% fat), or high‐polyunsaturatedfat (20% fat) diet at 21 days of age. A single dose of7,12‐dimethylbenz[at]anthracene (DMBA, 10 mg) was administered intragastrically at 50 days of age. Two studies were performed. One tested the effectiveness of antiestrogen treatment (either tamoxifen or analog II) on tumor development when it was given one week prior to and one week after DMBA treatment in animals consuming a high‐polyunsaturated fat diet. The second six‐week study tested the antiestrogen effectiveness in arresting tumor growth and in producing regressions of established DMBA‐induced tumors in rats consuming various levels and types of fat.

The results of these studies indicate that both antiestrogens employed reduced the rate of growth and increased the number of regressions of established DMBA‐induced tumors. In general, this was true in animals fed diets with a high content of either saturated or polyunsaturated fats and to a lesser extent in animals fed a low‐fat diet. Tamoxifen produced a somewhat greater reduction in the growth of established tumor than did analog II. However, analog II, which is a more biologically “pure” antiestrogen, reduced the incidence of animals with mammary tumors and total tumor burden when administered one week beforeandone week after DMBA dosing. Tamoxifen, which is a partial estrogen‐agonist, did not alter tumor incidence, but it did reduce the total tumor burden under these same experimental conditions. We concluded that estrogens may be partially responsible for the observed dietary fat enhancement of breast tumor development.     

S-allylcysteine, a garlic constituent, inhibits 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis

The effect of S-allylcysteine (SAC), a water-soluble garlic constituent, on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis was investigated in male Syrian hamstes. Forty hamsters were divided into 4 groups of 10 animals. The right buccal pouches of the animals in Group I were painted with a 0.5% solution of DMBA in liquid paraffin three times a week. The animals in Group II were painted with DMBA as in Group I and, in addition, received 200 mg/kg body wt p.o. SAC three times a week on days alternate to DMBA application. Group III animals received SAC as in Group II. Group IV animals received neither DMBA nor SAC and served as the control. The hamsters were killed after an experimental period of 14 wk. Measurement of lipid peroxidation, the antioxidant enzymes superoxide dismutase (SOD) and catalase, in the buccal pouch mucosa, liver, and circulation was used to monitor the chemopreventive potential of SAC. All hamsters painted with DMBA alone developed tumors identified histologically as well-differentiated squamous cell carcinomas. In hamsters bearing DMBA-induced buccal pouch tumors, diminished lipid peroxidation in the tumor tissue was accompanied by decreased activities of SOD and catalase, whereas in the liver and circulation, enhanced lipid peroxidation was associated with compromised antioxidant defenses. Administration of SAC suppressed the incidence of DMBA-induced HBP tumors as revealed by the absence of carcinomas. Histologically, only keratosis was observed. SAC modulated DMBA-induced decreased susceptibility of the HBP to lipid peroxidation while simultaneously enhancing SOD and catalase activities, whereas in the liver and circulation, SAC decreased the extent of lipid peroxidation and significantly enhanced antioxidant activities. We suggest that SAC exerts its chemopreventive effects by modulating lipid peroxidation and enhancing antioxidant activities in the target organ as well as in the liver and circulation.     

Luteolin Supplementation Modulates Mammary Tumor Growth in C3H Mice Fed Diet with High- and Low-Fat Content

In this study we investigated the effects of luteolin supplementation (0.05% w/w) on mammary tumor growth in C3H mice, a strain of mouse mammary tumor virus negative, fed either high-fat (45% fat of energy) or low-fat diet (15% fat of energy). Animals (n = 12/group) were allocated into 4 experimental groups (low-fat diet, low-fat diet + luteolin supplementation, high-fat diet, high-fat diet + luteolin supplementation). Experimental diet were fed for 13 wk and 7,12-dimethylbenz[a]anthracene was administered once a week for 6 wk starting at Week 1 to induce mammary tumors. Study results showed that animals on low-fat diet supplemented with luteolin exhibited longer tumor latency and lower tumor weights and sizes compared to the other groups. Animals fed high-fat diet showed increased serum IGF-1 levels and the elevated mammary tissue expression of Ki-67, IRS-1, pp38, Cdk4, and Cdk6. Luteolin inhibited IRS-1, Cdk4, and Cdk6 expression in high-fat fed animals. The expression of pp38, cyclinD1, and Bcl-xL was suppressed by luteolin supplementation both in the low-fat and high-fat diet groups. These results suggest that excess energy supply increases the risk of mammary tumor formation and luteolin suppresses tumor formation regardless of dietary fat content through its cell cycle regulatory and proapoptotic activity.     

Influence of dietary fat intake on local recurrence and progression of metastases arising from MDA-MB-435 human breast cancer cells in nude mice after excision of the primary tumor.

This study was performed to evaluate the effect of dietary fat on the recurrence and metastasis of human breast cancer solid tumors growing in nude mice after surgical excision of the primary tumor. Female nude mice were fed either a high- (23% corn oil) or a low-fat (5% corn oil) diet, and 7 days later 1 x 10(6) MDA-MB-435 human breast cancer cells were injected into a thoracic mammary fat pad. Tumors at the injection site grew more rapidly in the animals fed the high-fat diet. Nineteen of 30 animals in each dietary group had tumors with a surface are > or = 1 cm2 within 10 weeks of injection, at which point the tumors were excised and the animals were followed for another eight weeks. Tumors recurred at the excision site in 8 of 19 animals fed the high-fat diet and in 9 of 19 animals fed the low-fat diet; however, the growth rate was more rapid in the group fed the high-fat diet. Lung metastases occurred with similar frequency in the two groups with local recurrences, but with a positive correlation between recurrent tumor weight (greater in the animals fed the high-fat diet) and the severity of lung metastatic involvement. In the mice without recurrence, 4 of 11 (36%) animals in the group fed the high-fat diet had macroscopic lung metastases compared with only one mouse, with minimal involvement, in the group fed the low-fat diet.     

Inhibition of 7,12-dimethylbenz[a]anthracene-induced lipid peroxidation and mammary tumor development in rats by vitamin E in conjunction with selenium.

The effects of combined dietary vitamin E supplementation and a relatively low increase in selenium levels on 7,12-dimethylbenz[a]anthracene (DMBA) induction of lipid peroxidation in the short term and development of mammary tumors in the long term were investigated in female Sprague-Dawley rats. Control animals were fed the basal diet (20 mg/kg vitamin E and 0.6 mg/kg selenium) throughout the experiment. Three other groups received a high vitamin E diet (235 mg/kg vitamin E and 0.6 mg/kg selenium) at different times, the first two from three weeks after DMBA treatment and the other throughout the experiment. When the vitamin E diet with selenium supplementation was applied until three weeks after DMBA or until the termination of the experiment, tumor yields (tumors per rat) were significantly inhibited compared with the control group. On the other hand, delaying the supplementation of vitamin E until three weeks postcarcinogen produced no prophylactic effect. The elevation of lipid peroxidation levels observed immediately after DMBA administration was also significantly inhibited in both mammary fat pads and livers of animals in the high vitamin E group. It was therefore concluded that the inhibitory effect of vitamin E in combination with selenium on tumorigenesis might be causally related to reduction of carcinogen treatment associated with lipid peroxidation, the latter presumably playing an important role in DMBA-induced mammary carcinogenesis.     

Modulation of xenobiotic-metabolizing enzymes and redox status during chemoprevention of hamster buccal carcinogenesis by bovine lactoferrin

OBJECTIVE: Chemoprevention by dietary constituents has emerged as a novel approach to control oral cancer incidence. We therefore evaluated the chemopreventive efficacy of bovine milk lactoferrin (bLF) on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. METHODS: Hamsters were divided into four groups. The right buccal pouches of animals in groups 1 and 2 were painted with 0.5% DMBA three times a week for 14 wk. Animals in group 2, received in addition, basal diet containing 0.2% bLF. Group 3 animals were given 0.2% bLF alone. Group 4 animals served as control. The status of carcinogen-metabolizing enzymes, the extent of lipid peroxidation and glutathione-dependent antioxidants in the buccal pouch and liver as well as bone marrow micronuclei incidence were used as biomarkers. RESULTS: All the hamsters painted with DMBA alone for 14 wk, developed HBP carcinomas that showed diminished lipid peroxidation and increased activities of carcinogen-metabolizing enzymes and antioxidants with enhanced bone marrow micronuclei. In the liver of tumor bearing animals, the increase in phase I enzymes and lipid peroxidation was accompanied by reduced activities of antioxidant and phase II detoxification enzymes. Administration of bLF decreased the incidence of DMBA-induced micronuclei and HBP carcinomas by decreasing phase I enzymes, modulating lipid peroxidation and enhancing antioxidant and phase II enzyme activities. CONCLUSION: The chemopreventive effects of bLF is mediated by reducing DMBA-induced genotoxicity and modulating carcinogen-metabolizing enzymes and oxidant-antioxidant profile in the target organ as well as in the liver.     

Dietary Genistein Increased DMBA-Induced Mammary Adenocarcinoma in Wild-Type,but Not ERαKO,Mice

Dietary supplements containing concentrates of plant-derived estrogens are being increasingly used by consumers as alternatives for hormone replacement therapy, for treatment of menopausal symptoms, and as cancer preventives. The effect of dietary genistein on dimethylbenz[a]anthracene (DMBA)-induced mammary tumor development was investigated in wild-type (ERαWT) and estrogen receptor-α knockout (ERαKO) mice. ERαWT and ERαKO mice were fed a casein-based diet containing 0 or 1 g genistein/kg diet from weaning. Tumors were induced by oral administration of DMBA and subscapular implantation of medroxyprogesterone acetate. No tumors were observed in ERαKO mice. In ERαWT mice, dietary intake of genistein influenced tumor development, enhancing anaplasia of mammary cancer. Mice consuming genistein expressed malignant mammary adenocarcinoma, whereas benign adenomas were observed in mice fed the control diet. Dietary intake was also influenced by genistein, with ERαWT and ERαKO mice fed genistein consuming less food (p < 0.0001) and subsequently weighing less than mice fed the control diet (p < 0.0001). Significant differences in food intake by genotype were also observed (p = 0.0017), with ERαKO mice consuming less than ERαWT mice. Overall, this study found no protective effect of genistein on DMBA-induced mammary tumors in mice and suggests a potential adverse effect on tumor development when high levels of genistein are consumed.     

Dietary genistein increased DMBA-induced mammary adenocarcinoma in wild-type, but not ER alpha KO, mice.

Dietary supplements containing concentrates of plant-derived estrogens are being increasingly used by consumers as alternatives for hormone replacement therapy, for treatment of menopausal symptoms, and as cancer preventives. The effect of dietary genistein on dimethylbenz[a]anthracene (DMBA)-induced mammary tumor development was investigated in wild-type (ER alpha WT) and estrogen receptor-alpha knockout (ER alpha KO) mice. ER alpha WT and ER alpha KO mice were fed a casein-based diet containing 0 or 1 g genistein/kg diet from weaning. Tumors were induced by oral administration of DMBA and subscapular implantation of medroxyprogesterone acetate. No tumors were observed in ER alpha KO mice. In ER alpha WT mice, dietary intake of genistein influenced tumor development, enhancing anaplasia of mammary cancer. Mice consuming genistein expressed malignant mammary adenocarcinoma, whereas benign adenomas were observed in mice fed the control diet. Dietary intake was also influenced by genistein, with ER alpha WT and ER alpha KO mice fed genistein consuming less food (p < 0.0001) and subsequently weighing less than mice fed the control diet (p < 0.0001). Significant differences in food intake by genotype were also observed (p = 0.0017), with ER alpha KO mice consuming less than ER alpha WT mice. Overall, this study found no protective effect of genistein on DMBA-induced mammary tumors in mice and suggests a potential adverse effect on tumor development when high levels of genistein are consumed.     

Effects of dietary fat on long-term growth and mammary tumorigenesis in female Sprague-Dawley rats given a low dose of DMBA

The effects of dietary fat on experimental mammary cancer have typically been observed in relatively young animals. However, in human populations, breast cancer incidence and mortality are highest in postmenopausal women. To develop an animal model that stimulates the human situation more closely, female Sprague-Dawley rats were given a relatively small dose (1.5 mg) of 7,12-dimethylbenz[a]anthracene (DMBA) at 50 days of age while on a semipurified diet containing 3% sunflower-seed oil. One week later, half of the 70 rats were transferred to a diet containing 20% sunflower-seed oil. Very few mammary lesions appeared until about 35 weeks after administration of DMBA, at which time palpable mammary nodules began to appear in many of the animals on the high-fat diet. More than half of the animals in this group had developed nodules by Week 41, whereas the other half of the animals on the low-fat diet developed nodules by Week 46. Rats on the high-fat diet gradually became much more obese than those on the low-fat diet and were significantly heavier at the time they developed lesions. The incidence of nodules continued to increase in both groups and reached 100% in the group fed the high-fat diet by Week 55, with a 70% incidence of adenocarcinomas. At this time, 79% of the animals on the low-fat diet had palpable nodules without a plateau in incidence being reached. On autopsy, adenocarcinomas were found in 57% of animals on the low-fat diet.(ABSTRACT TRUNCATED AT 250 WORDS)     

Determination of degree of energy restriction necessary to reduce DMBA-induced mammary tumorigenesis in rats during the promotion phase

This study was designed to determine the degree of energy restriction necessary to achieve significant inhibition of mammary tumor promotion in rats treated with 7,12-dimethylbenz[a]anthracene (DMBA). A control group of rats was fed a diet containing 5% corn oil ad libitum. Four other groups were pair-fed to the controls; these rats were subjected to energy restriction of 10, 20, 30, or 40%. Weight gains among the groups were proportional to energy intake. The differences in weight were due primarily to reductions in body fat stores. Tumor incidence was reduced slightly by 20% calorie restriction and significantly by 30 and 40% restriction. There were also reductions in number of tumors per tumor-bearing rat and in mean tumor weight. The groups subjected to 30 and 40% energy restriction had significantly reduced serum levels of insulin in the fasting state. These data suggest that body weight, body fat, and fasting serum insulin correlate with susceptibility to mammary tumor promotion and that insulin may be a growth factor for DMBA-induced tumors.     

Effects of dietary protein, fat and energy intake during an initiation phase study of 7,12-dimethylbenz[a]anthracene-induced breast cancer in rats

A factorial experiment was conducted to examine the effects of dietary protein (8, 16, 32% of energy from casein) and dietary fat (12, 24, 48% of energy from corn oil) on the initiation of 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast carcinogenesis in rats. Forty weanling female Sprague-Dawley rats were assigned to each of nine diets fed ad libitum. After 4 wk each rat received DMBA (20 mg/kg) via gastric intubation. For an additional 22 wk after carcinogen administration all rats consumed a diet containing 16% of dietary energy from protein and 24% from fat. Dietary fat, protein and ad libitum energy consumption exhibited statistically significant effects on final tumor prevalence, but interactive effects were not found. At necropsy, rats fed corn oil at 12, 24 and 48% of energy prior to DMBA administration showed tumor prevalences of 58, 58 and 85% with 116, 153 and 231 total tumors, respectively. The data indicate a significant nonlinear effect of dietary fat. Corresponding numbers for rats fed casein at 8, 16 and 32% of energy prior to DMBA were prevalences of 79, 65 and 59%, with total tumor counts of 194, 144 and 162. Higher dietary protein during the initiation phase was associated with a significant reduction in tumor prevalence, which was most striking between 8 and 16% of energy from protein. In addition, results of multiple logistic regression showed that tumorigenesis was increased with greater ad libitum energy intake. The odds of a tumor at necropsy were multiplied by 1.19 for each kilocalorie increase in ad libitum energy intake averaged over the post-DMBA phase of the experiment. An additional six weanling rats fed each diet for 4 wk were killed for assay of hepatic carcinogen metabolizing enzymes at the time corresponding to DMBA administration in the initiation experiment. Both protein and fat showed independent effects on the activity of several enzymes. However, enzyme activity did not suggest a unifying mechanism whereby these nutrients influence DMBA-induced mammary carcinogenesis.     

Retardation of experimental oral cancer development by retinyl acetate

Sixty young adult Syrian hamsters were divided into five groups. Group 1 and Group 2 animals were treated with 0.25% dimethylbenz(a)anthracene (DMBA), painted on their left buccal pouches thrice weekly for 20 weeks. Starting at 12 weeks, at which time there was clinical evidence of leukoplakia and initial tumor formation, Group 2 animals received 10 mg retinyl acetate 3 times/week in a 5% solution in peanut oil, while Group 1 animals received only peanut oil. Two animals in Group 1 and two animals in Group 2 were sacrificed weekly from week 12 to week 20. Left buccal pouches were examined, tumors were counted, and tumor size was measured. Group 3 animals were untreated controls, Group 4 animals were retinyl acetate controls, and Group 5 animals received only peanut oil. It was found that DMBA‐treated animals receiving retinyl acetate from week 12 to week 20 developed fewer tumors, and their average tumor size was less than that in DMBA ‐treated animals not receiving retinyl acetate. It appears that retinyl acetate, administered systemical‐ly, can retard tumor development even after leukoplakia has been established and tumors have begun to develop.     

Energy restriction modulates the development of advanced preneoplastic lesions depending on the level of fat in the diet

Our objective was to investigate the ability of preneoplastic colonic lesions at different stages of development to respond to the growth-retarding effects of energy restriction (ER). Male Fischer 344 rats were given three injections of azoxymethane (15 mg/kg s.c.) and fed a high-fat corn oil diet for 16 weeks. This duration allowed aberrant crypt foci (ACF) to develop and acquire different growth states. ACF growth was assessed by enumerating the number of crypts per focus. At Week 16, 10 animals were killed and their colons were enumerated for ACF (baseline). The remaining animals were then allocated to four dietary groups: high-fat (23% wt/wt), low-fat (5% wt/wt), high-fat energy-restricted (HFER), or low-fat energy-restricted (LFER). After the animals were fed the experimental diets for six weeks, ER decreased the total number of ACF regardless of the level of fat. At Week 12, the LFER diet retarded the appearance of advanced ACF, but this was not the case for the HFER diet. Consequently, the level of fat was identified as the significant variable in affecting the number of ACF with different crypt multiplicity. The animals fed the LFER diet had the fewest tumors and microadenomas per rat. The HFER diet was ineffective in modulating tumor outcome. To our knowledge, these findings are the first to suggest that ER modulated the development of advanced ACF and colonic tumors depending on the level of fat in the diet.     

Do beans and oat bran add to the effectiveness of a low-fat diet?

The effects of consuming an increased amount of soluble fibre as oat bran or beans were examined in 40 free-living hypercholesterolaemic men and women. The subjects were initially established on a low-fat background diet (29% of energy from fat) and then 55 g low-fibre oat bran, 55 g high-fibre oat bran or 80 g mixed cooked beans were added to their diet in random order for 6 week periods. Body weight and overall composition of the diet did not change. Plasma cholesterol and low-density lipoprotein cholesterol (LDL-C) were unchanged. High-density lipoprotein cholesterol (HDL-C) was significantly higher on all three intervention diets than on the lower fibre run-in diet. Supplementation of a moderately low-fat diet with palatable quantities of oat bran or beans without changing the overall fat intake does not appear to significantly lower cholesterol but may have a benefit by increasing HDL-C and reducing the ratio of LDL-C to HDL-C.     

Acceleration of papilloma growth in mice fed high-fat diets during promotion of two-stage skin carcinogenesis

The effect of feeding a high-fat diet during the promotion phase of skin tumorigenesis was assessed in SENCAR mice. Tumors were initiated on the backs of mice by application of 10 nmol 7,12-dimethylbenz[a]anthracene (DMBA); the tumors were then promoted beginning one week later with twice weekly treatments of 2 micrograms 12-O-tetradecanoylphorbol-13-acetate (TPA) each in 0.2 ml acetone. Control diet containing 5% corn oil was fed from four weeks before until one week after DMBA treatment in all groups. A high-fat diet (24.6% corn oil) was fed from one week after DMBA treatment; the other groups continued on the control diet. Mice were fed ad libitum, and those given the high-fat diet consumed more calories early in the study than the controls did. Treatment with TPA increased calorie consumption throughout the study. Body weights were elevated in mice fed high-fat diets and reduced by TPA treatment. The average number of papillomas per mouse did not differ between the low- and high-fat groups, but papillomas grew more rapidly on the mice fed a high-fat diet than those fed a low-fat diet. The feeding of a high-fat diet following DMBA treatment, in the absence of TPA administration, did not result in promotion of skin tumors. Therefore, a high-fat diet acted as a copromoter of skin tumors in SENCAR mice.     

Lack of a Significant Effect of Arctiin on Development of 7,12-dimethylbenz(a)anthracene-induced Mammary Tumors in Ovariectomized Sprague-Dawley Rats

Arctiin, a plant lignan, is metabolized to hormone-like compounds with weak estrogenic and antioxidative activity in experimental animals and man. To clarify its influence on mammary carcinogenesis, female rats were administrated 7,12-dimethylbenz(a)anthracene (DMBA) once, and when the incidence of palpable mammary tumors reached 50%, subjected to ovariectomy (OVX) and divided into tumor-bearing [DMBA-Tumor (+)] and no-tumor-bearing [DMBA-Tumor (?)] groups, subgroups of each then being fed soybean-free diet containing 0, 40, 200, and 1000 ppm of arctiin for 31 wk. The incidence and multiplicity of palpable tumors in the 200 ppm DMBA-Tumor (+) subgroup from week 12 of arctiin treatment tended to be decreased as compared to the 0 ppm subgroup and at terminal sacrifice, the volume of histopathologically defined mammary tumors was decreased in the 40 ppm DMBA-Tumor (?) subgroup, but again without statistical significance. In conclusion, weak inhibitory effects of arctiin on DMBA-induced mammary tumor development were suggested in OVX rats, but any further assessment is needed to obtain conclusive results.     

Lack of a significant effect of arctiin on development of 7,12-dimethylbenz(a)anthracene-induced mammary tumors in ovariectomized Sprague-Dawley rats

Arctiin, a plant lignan, is metabolized to hormone-like compounds with weak estrogenic and antioxidative activity in experimental animals and man. To clarify its influence on mammary carcinogenesis, female rats were administrated 7,12-dimethylbenz(a)anthracene (DMBA) once, and when the incidence of palpable mammary tumors reached 50%, subjected to ovariectomy (OVX) and divided into tumor-bearing [DMBA-Tumor (+)] and no-tumor-bearing [DMBA-Tumor (-)] groups, subgroups of each then being fed soybean-free diet containing 0, 40, 200, and 1000 ppm of arctiin for 31 wk. The incidence and multiplicity of palpable tumors in the 200 ppm DMBA-Tumor (+) subgroup from week 12 of arctiin treatment tended to be decreased as compared to the 0 ppm subgroup and at terminal sacrifice, the volume of histopathologically defined mammary tumors was decreased in the 40 ppm DMBA-Tumor (-) subgroup, but again without statistical significance. In conclusion, weak inhibitory effects of arctiin on DMBA-induced mammary tumor development were suggested in OVX rats, but any further assessment is needed to obtain conclusive results.     

Kahweol and cafestol: inhibitors of hamster buccal pouch carcinogenesis

Kahweol and cafestol, two compounds extracted from green coffee beans, were tested for cancer chemopreventive activity. For the experiment, 60 hamsters were divided into three equal groups and placed on one of three diets. The animals in Group I received a normal diet, whereas the animals in Groups II and III received the same diet supplemented with a 50:50 mixture of kahweol and cafestol. The content of the kahweol and cafestol mixture in these two diets was 0.2 g/kg of food (Group II) and 2.0 g/kg of food (Group III). After the hamsters adjusted to their respective diets, 16 hamsters from each group were selected. The left buccal pouches of these animals were painted three times weekly with a 0.5% solution of 7,12-dimethylbenz[a]anthracene (DMBA) in mineral oil. The 12 remaining hamsters were used as controls. The left buccal pouches of these animals were painted three times weekly with mineral oil. After 13 weeks (39 applications) the hamsters were killed. Multiple tumors were common in animals treated with DMBA; however, the animals receiving kahweol and cafestol in the diet (2 g/kg of food) exhibited a 35% reduction in tumor burden. Further comparisons between Groups I and III showed that this reduction in tumor burden was due to a decrease in tumor number. The results for Group II were inconclusive. Some reduction in tumor number was found, but this was offset by an increase in the size of the tumors.     

Decreased growth of human prostate LNCaP tumors in SCID mice fed a low-fat, soy protein diet with isoflavones

Epidemiological studies suggest that high intake of dietary fat is a risk factor for the development of clinical prostate cancer. Soy protein has also been proposed to play a role in the prevention of prostate cancer, and one of the isoflavones in soy protein, genistein, inhibits the growth of human prostate cancer cell lines in vitro. This study was designed to evaluate whether altering dietary fat, soy protein, and isoflavone content affects the growth rate of a human androgen-sensitive prostate cancer cell line (LNCaP) grown in severe-combined immunodeficient (SCID) mice. SCID mice were randomized into four dietary groups: high-fat (42.0 kcal%) + casein, high-fat (42.0 kcal%) + soy protein + isoflavone extract, low-fat (12.0 kcal%) + casein, and low-fat (12.0 kcal%) + soy protein + isoflavone extract. After two weeks on these diets, the mice were injected subcutaneously with 1 x 10(5) LNCaP tumor cells and placed in separate cages (1 mouse/cage) to strictly control caloric intake. Isocaloric diets were given 3 days/wk, and tumor sizes were measured once per week. The tumor growth rates were slightly reduced in the group that received the low-fat + soy protein + isoflavone extract diet compared with the other groups combined (p < 0.05). In addition, the final tumor weights were reduced by 15% in the group that received the low-fat + soy protein + isoflavone extract diet compared with the other groups combined (p < 0.05). In this xenograft model for prostate cancer, there were statistically significant effects on tumor growth rate and final tumor weight attributable to a low-fat + soy protein + isoflavone extract diet.     

Assessment of the effect of fat-modified foods on diet quality in adults, 19 to 50 years, using data from the Continuing Survey of Food Intake by Individuals

Fat-reduction strategies and the role of fat-modified foods in the US diet were assessed using a nationally representative survey: the 1996 US Department of Agriculture Continuing Survey of Food Intakes by Individuals. A sample of 878 men and 853 women was included. The sample was divided into low fat and high fat based on the Dietary Guideline's cutoff poin of 30% or less of energy from total fat. The survey sample was further stratified in nonusers, low-users or high-users of fat-modified foods. Approximately 10% of 7,000 foods were classified as fat-modified. There was a 400 to 500 kcal difference in energy intake of individuals consuming low-fat compared with high-fat diets. Adults who were users of fat-modified foods consumed more nutrient-dense diets, with higher intakes of vitamin A, folate, and iron. Not all fat-reduction strategies were equally effective in reducing fat and maintaining nutrient intake. Nonusers of fat-modified foods who consumed a low-fat diet tended to do so by substituting carbohydrate, in part from carbonated beverages, for fat. Both men and women consuming a low-fat diet had lower average BMIs; this difference between individuals consuming low-fat vs high-fat diets was significant for women who were high-users of fat-modified foods. The data suggest that a low-fat diet with high use of fat-modified foods may be one strategy for achieving adequate nutrient intake while maintaining weight in the desirable BMI range of 19 to 25.