Effects of dietary selenium on DMBA-induced carcinogenesis in rats fed a diet high in mixed fats

The effects of selenium intake on 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinogenesis were examined in rats fed a diet high in mixed fats and representative of that consumed in North America. Six groups of 20 rats were fed an AIN-76 diet modified to contain 20% fat from lard:corn oil (3:1 wt/wt) and various amounts of selenium (0.1, 0.035, 0.1, 1.0, 2.0 or 4.0 mg Se/kg diet). At wk 5, animals in groups 2-6 were dosed with 4.32 mg of DMBA. Serum clinical parameters and the activities of plasma selenium-dependent and total glutathione peroxidase (GSHPx), erythrocyte GSHPx and superoxide dismutase (SOD) were determined every 4 wk for 25 wk. The extent of lipid peroxidation was determined by measuring urinary malondialdehyde during wk 13 and 24, and erythrocyte malondialdehyde at wk 25. Erythrocyte GSHPx was found to be a better indicator of selenium status than plasma activity, while SOD did not vary with dietary selenium. The group of animals fed 4.0 mg Se/kg diet had reduced numbers of tumors (P less than 0.01), but this reduction was associated with evidence of chronic selenium toxicity. Variations in GSHPx activity with dietary selenium did not result in differences in tumor incidence, nor in changes in lipid peroxidation in the other groups. Thus, nontoxic levels of selenium do not appear to offer any protective effect during carcinogenesis in rats fed a casein-based diet similar in fat content to that consumed by North Americans.     

Prospective study on selenium and antioxidant status during dmba-induced mammary carcinogenesis

The purpose of this study was to examine selenium (Se) and antioxidant status of rats during the development of DMBA-induced mammary carcinogenesis and to determine whether there are differences between DMBA-treated rats that remained free of tumors (NT group, n=23), animals that developed tumors (WT group, n=7) and vehicle-treated control rats (n=20). All animals were fed the recommended amount of Se (0.1 mg/kg) in a high fat (20%) diet. The activities of Se-dependent glutathione peroxidase (SeGSHPx) and Cu,Zn-superoxide dismutase (SOD) were determined in plasma and erythrocytes every 2 wks for the 21 wk duration of the experiment. Lipid peroxidation was assessed by measuring urinary malondialdehyde. SeGSHPx activity was lower in WT rats, before the appearance of tumors, compared to both NT and control rats. In contrast, SOD activity was reduced in DMBA-treated rats compared to control animals, but there were no differences between NT and WT rats. These changes in enzyme activity and the presence or absence of tumors did not affect lipid peroxidation.     

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.     

The combined effects of dietary protein and fat intake during the promotion phase of 7,12-dimethylbenz(a)anthracene-induced breast cancer in rats

A 3 X 3 factorial experiment was conducted to examine the effects of dietary protein (8, 16 or 32% of energy from casein) and dietary fat (12, 24 or 48% of energy from corn oil) on the promotion phase of 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast carcinogenesis in rats. A purified diet with protein and fat supplying 16 and 24% of energy, respectively, was fed to 360 rats. After 4 wk each rat received DMBA (20 mg/kg) via gastric intubation. Forty rats were then randomly assigned to each of the nine dietary treatments for 28 wk. We observed no effects of protein or interactions between protein and fat on mammary tumorigenesis. At necropsy, rats fed diets containing 12, 24 and 48% of energy from corn oil following DMBA administration showed tumor prevalences of 53, 60 and 70% with 109, 127 and 140 total tumors, respectively. Linear logistic statistical modeling indicated that each doubling of dietary fat concentration multiplied the odds of finding a tumor of any histologic type at necropsy by 1.52. Dietary fat had no significant effects on the prevalence of adenomas or fibroadenomas, whereas those fed corn oil at 12, 24 and 48% of dietary energy showed adenocarcinoma prevalences of 34, 41 and 52% with total adenocarcinoma counts of 66, 75 and 96, respectively. Our results suggest that increasing dietary fat enhanced the promotion of DMBA-induced breast carcinogenesis over a wide range of protein intake.     

Effects of dietary lipid saturation on prolactin secretion, carcinogen metabolism and mammary carcinogenesis in rats

Isoenergetic diets containing 20% corn oil, 20% beef tallow, or an equal mixture of 10% corn oil and 10% beef tallow (mixed fat) were fed to 30 rats per diet for 28 weeks following weaning. DMBA [7,12-dimethylbenz(a)anthracene] was administered (1.75 mg/100 g body weight) in a single oral dose after 4 weeks of feeding. After 28 weeks, 70% of the rats fed corn oil had mammary tumors versus 47% for mixed fat and 30% for tallow. Diet had no effect on the number of tumors per tumor-bearing rat or the proportion of tumors that were adenocarcinomas. Other rats assigned to each of the three diets were killed at the time corresponding to DMBA administration for examination of hepatic mixed-function oxidase activity. NADPH cytochrome c reductase activity and cytochrome P-450 content were higher in rats fed corn oil or mixed fat rather than tallow. However, no significant differences in aryl hydrocarbon hydroxylase, glutathione transferase, and uridine-diphosphoglucuronide transferase activities were observed. The effects of dietary fat saturation on enzyme activity failed to show a clear association with DMBA carcinogenesis. In other rats assigned to the three dietary treatments for 4 or 16 weeks, lipid saturation did not change serum prolactin (PRL) concentrations during diestrus or proestrus. PRL secretion was examined following a provocative stimulus (perphenazine) in rats fed the experimental diets for 4 or 10-22 weeks. Although perphenazine increased serum PRL and depleted the pituitary of PRL, differences in dietary lipid saturation caused no significant changes in these indices. These data show that the incidence of mammary tumors in rats fed high fat diets (20% by weight) was greater in those fed corn oil compared to beef tallow. The effect of dietary lipid source on tumorigenesis was not associated with changes in carcinogen-metabolizing enzyme activity or PRL secretion.     

The combined effects of dietary protein and fat on 7,12-dimethylbenz(a)anthracene-induced breast cancer in rats

A 3 X 3 factorial experiment was conducted to examine how protein content (8, 16, 32% of kilocalories from casein) and fat content (12, 24, 48% of kilocalories from corn oil) interact to influence 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast carcinogenesis in rats. Forty weanling Sprague-Dawley rats were assigned to each of 9 diets fed ad libitum. After 4 weeks each rat received DMBA (20 mg/kg) via gastric intubation. No substantial statistical interactions of protein and fat were observed on tumor incidence. Increasing dietary corn oil increased the percentage of rats with palpable tumors. Rats fed diets containing 12, 24 and 48% of kilocalories from corn oil showed 35, 49 and 70% tumor prevalence at necropsy, and the total number of tumors per fat level was 65, 81 and 182, respectively. Each doubling of dietary fat concentration approximately doubled the odds of a rat developing a tumor. Multiple tumors were more common with the highest corn oil intake. The odds of finding a second tumor in rats with one tumor increased by a factor of 7.5 when fat kilocalories were increased from 24 to 48% compared to a decrease of one-third when fat kilocalories were increased from 12 to 24%. Dietary corn oil significantly increased the prevalence of adenocarcinomas and adenomas but not fibroadenomas. Dietary protein did not significantly affect tumor prevalence. However, tumors palpated in rats fed 16% of kilocalories as protein regressed more frequently than in rats fed low or high protein diets. Multiple logistic-regression results indicate that, in addition to the response to dietary corn oil, tumorigenesis was increased in rats with greater ad libitum food consumption. This conclusion is supported by reanalysis that used direct rate adjustment and average partial association tests.     

Dietary olive and safflower oils in promotion of DMBA-induced mammary tumorigenesis in rats

Interpretation of studies comparing the efficacy of different dietary fat sources in promoting 7,12-dimethylbenz[a]-anthracene (DMBA)-induced rat mammary tumorigenesis often ignores the fact that about 4% (wt/wt) linoleic acid (18:2n-6) is required for optimal tumor promotion. We therefore fed DMBA-intubated or placebo-intubated female, Sprague-Dawley rats 20% fat diets containing 18:2n-6 (wt/wt) from either high-linoleic safflower oil (SL, 14.6% 18:2n-6), high-oleic safflower oil (SO, 3.4% 18:2n-6), olive oil (OO, 1.1% 18:2n-6), or OO supplemented with 18:2n-6 (OL, 3.4% 18:2n-6) for 16 weeks. Results indicated that OO-fed rats had longer tumor-free time, fewer tumors per rat, and lower tumor incidence compared with SO and OL. Addition of 2.3% 18:2n-6 to OO enhanced tumor promotion (p less than 0.04); SL, SO, and OL demonstrated similar tumor-enhancement effect. About 74% of observed mammary tumors were adenocarcinomas; a greater number of tumors appeared in the thoracic and inguinal than in the cervical and abdominal regions irrespective of diet. These results indicate that once an optimal amount of linoleic acid is provided in the diet, oleic- or linoleic-rich oils have similar effects on promotion of mammary tumors in the rat.     

Mammary tumor lipids and plasma lipoproteins in DMBA-intubated rats fed olive or safflower oils

The effects of feeding olive and safflower oils on lipid and fatty acid composition of mammary tumors, plasma lipids and lipoproteins, and the nuclear magnetic resonance (NMR) spectra of plasma were investigated in rats. 7-12-Dimethylbenz[a]anthracene (DMBA)- and placebo-intubated male Sprague-Dawley rats were fed 20% fat diets containing 18:2n-6 (wt/wt) from either high-linoleic safflower oil (SL, 14.6% 18:2n-6), high oleic safflower oil (SO, 3.4% 18:2n-6), olive oil (OO, 1.1% 18:2n-6), or olive oil supplemented with 18:2n-6 (OL, 3.4% 18:2n-6) for 16 weeks. Our result indicated that tumor composition of 18:1n-9 and 18:2n-6 reflected the diet, but tumor neutral lipid (NL) was more reflective of diet than was tumor phospholipid (PL). The 20:4n-6 content of tumor PL was constant in all of the dietary groups despite threefold higher levels of 18:2n-6 in tumor PL from animals fed SL than from those fed SO, OO, or OL diets. This suggests a possible feedback inhibition of delta 6-desaturase by the higher content of 18:2n-6 associated with SL feeding No diet effects were obtained for tumor total lipid, NL, PL, cholesterol, and triglyceride contents. Plasma lipoprotein changes were more reflective of diet than tumorigenesis except for apolipoprotein-E, which was lower, and for very low-density lipoprotein cholesterol and low-density lipo protein, which were higher in tumor-bearing rats. Plasma NMR analysis indicated no difference in the average line widths of the methyl and methylene resonances for tumor-bearing and nontumor-bearing rats fed any of the diets.     

The effect of diet, exercise and 7,12-dimethylbenz(a)anthracene on food intake, body composition and carcass energy levels in virgin female BALB/c mice

This study investigated the effect of diet, exercise and , 7,12-dimethylbenz(a)anthracene (DMBA), a mammary-tumor carcinogen, on food intake, energy consumption, body weight and body composition in virgin female BALB/c mice. Interactions were examined among three diet conditions (standard AIN-76A, restricted AIN-76A and high fat AIN-76A diet), two exercise conditions (with and without treadmill exercise) and two treatment conditions (carcinogen or corn oil sham). Mice were randomized to one of 12 groups at 6 wk of age; beginning at 8 wk of age, all mice received either 7,12-dimethylbenz(a)anthracene (1 mg/0.2 mL corn oil) or 0.2 mL of corn oil via gastric tube once each week for six consecutive weeks. Exercise in a rotating-drum treadmill was initiated at 10 wk of age and was increased to a final rate of 6 m/min for 60 min, 5 d/wk. Mice were killed at 24 wk of age, confirmed to be tumor-free and analyzed for protein and fat content, from which body energy was calculated. Energy consumption was highest in the standard diet-fed groups followed by the high fat diet-fed groups and the restricted diet-fed groups. The groups fed the standard diet and restricted diet had similar body weight and carcass energy. Exercise or DMBA treatment generally reduced food consumption, energy intake, body weight and carcass energy. In summary, diet, exercise and DMBA all had pronounced effects on energy consumption, which in turn affected body composition. These treatments may influence expression of breast cancer via their effects on body composition.     

Menhaden oil inhibited gamma-glutamyltransferase-positive altered hepatic foci in female Sprague-Dawley rats

Feeding menhaden oil, high in n-3 fatty acids, or a mixture of lard and corn oil with a polyunsaturated-to-monounsaturated fatty acid ratio of 1:1 was hypothesized to inhibit promotion of hepatocarcinogenesis in rats by decreasing hepatic prostaglandin (PG) levels. Ten-day-old female Sprague-Dawley rats were injected with diethylnitrosamine (DEN, 15 mg/kg body wt ip). At 4 wk of age, rats were fed fumonisin B1(50 mg/kg diet) for 5 wk in diets containing 14% lard + 6% corn oil, 10% lard + 10% corn oil, 14% menhaden oil + 6% corn oil, and 7% menhaden oil + 13% corn oil. Plasma alanine aminotransferase activity was 20% lower in rats fed 10% lard than in rats fed the other diets (P < 0.05). In menhaden oil-fed rats, total plasma cholesterol concentrations decreased 26% (P < 0.05) and hepatic phospholipid C20:5n-3, C22:5n-3, and C22:6n-3 fatty acid concentrations increased compared with lard-fed rats. Hepatic n-3 fatty acids were threefold greater in rats fed 10% lard than in rats fed 14% lard. The liver-associated natural killer cell activity in rats fed menhaden oil was 58% lower than in rats fed lard (P < 0.03). Rats fed lard had threefold (P < 0.05) greater area of _-glutamyltransferase-positive altered hepatic foci (AHF) than did rats fed menhaden oil. There was no significant difference in placental glutathione S-transferase-positive AHF among the groups. Hepatic PGF2alpha production was 60-80% greater in rats fed 14% lard than in rats fed the other diets (P < 0.05). Hepatic PGE2 was 48% less in rats fed 14%; menhaden oil than in rats fed 14% lard (P < 0.05). Although gamma-glutamyltransferase-positive focal area was inhibited by menhaden oil, only 14% menhaden oil inhibited PGE2. Feeding 10% lard inhibited PGF2alpha, but not the development of AHF. Therefore, decreased hepatic PGs did not explain the inhibition of carcinogenesis.     

麦胚黄酮类提取物对荷瘤大鼠的抗氧化作用

为研究由麦胚提取的黄酮类化合物对 7,12 二甲基苯蒽 (DMBA)诱发大鼠乳腺肿瘤的抑制作用 ,将出生 5 0天的雌性SD大鼠随机分为阴性对照组、阳性对照组、低剂量实验组和高剂量实验组。阳性及阴性对照组大鼠喂基础饲料 ,除阴性对照组外的 3组大鼠经灌胃给致癌剂DMBA(每只 15mg溶于 1 5ml的植物油中 ) ,低 高剂量实验组大鼠同时给含麦胚黄酮类提取物的饲料 (分别为 2和 10g kg) ,持续喂养 2 4周。结果表明 ,高剂量组大鼠乳腺肿瘤的发生率较阳性对照组显著降低 ,实验组大鼠血液及肝脏中谷胱甘肽过氧化物酶活性和超氧化物歧化酶活性较阳性对照组大鼠有明显增加 ,丙二醛含量下降。提示麦胚提取的黄酮类化合物对抗过氧化物酶的诱导作用可能是其对乳腺癌具有化学预防作用的机制之一。     

Growth of Dunning transplantable prostate adenocarcinomas in rats fed diets with various fat contents

The effects of dietary fat concentration (5 vs. 20% corn oil, 0.5 vs. 20% corn oil and fat-free vs. 20% corn oil) on the growth of the Dunning R3327-H (hormone-sensitive, well-differentiated, slow-growing) and R3327-150 (hormone-insensitive, anaplastic, rapidly growing) transplantable prostate tumor sublines were studied in Copenhagen x Fisher F1 male rats. Rats fed 5 vs. 20% corn oil or 0.5 vs. 20% corn oil showed no differences in either R3327-H or R3327-150 tumor growth. Fat-free diets had no effect on the growth of R3327-150 tumors. However, the mean weight of the R3327-H tumor at necropsy, 16 wk after implantation, was reduced by 40% in rats fed a fat-free diet compared with 20% corn oil (P less than 0.05). Energy intake, weight gain and the weight of the pituitary and prostate glands in rats bearing either tumor was lower in rats fed the fat-free diet than in those fed the 20% corn oil diet. There were no differences in serum prolactin, pituitary prolactin or serum testosterone associated with dietary fat concentration in any study. In summary, no differences in transplantable prostate tumor growth were seen over a wide range of lipid intake (0.5-20%), although a fat-free diet reduced the growth of the R3327-H prostate adenocarcinoma.     

Changes in colonic antioxidant status in rats during long-term feeding of different high fat diets.

The effects of dietary fat on antioxidant mechanisms in colon mucosa were examined using male Sprague-Dawley rats. Animals were fed one of four AIN-76A-based test diets differing in amount and type of fat. The basal diet (BD) contained 5% corn oil; the menhaden oil diet (MO) contained 1% corn oil and 19% menhaden oil; the corn oil diet (CO) contained 20% corn oil; and the beef tallow diet (BT) contained 1% corn oil and 19% beef tallow; all were adjusted to provide equal amounts of other nutrients per kilojoule. Homogenates of colon mucosa were assayed after 2 wk and 1, 3, 6 and 9 mo for activities of catalase (CAT), glutathione peroxidase (GSHPx), superoxide dismutase (SOD), glutathione-S-transferase, glutathione reductase (GSSGRx), and total glutathione (GSH) content. Activity of GSHPx was depressed in rats fed high fat diets compared with rats fed the low fat BD. Animals fed the BD and MO diets had higher levels of CAT and GSSGRx as compared with rats fed the CO and BT diets. Activities of SOD, GSSGRx and GSHPx, as well as GSH concentration, decreased over time. Ornithine decarboxylase activity was not induced by the high fat diets. Thiobarbituric acid-reacting substances were virtually undetectable. Thus, both type and amount of fat affected antioxidant mechanisms in colon mucosa without producing overt oxidative damage in the tissue.     

The influence of diet on the regression of the Walker carcinosarcoma 256 in rats

Regression of the Walker carcinosarcoma 256 has been observed in rats inoculated with 10(4) viable tumor cells. The regression was found to be affected by dietary composition. Tumors in rats fed a commercial laboratory diet (CLD) regressed after a 9-day initial growth period while tumors in rats fed a purified diet high in free fatty acids continued to grow. Diets with 20% corn oil promoted tumor regression, but rats fed diets containing 20% free fatty acids from corn oil had tumors that continued to grow. The nonsaponifiable fraction (NSF) of corn oil appeared to promote tumor regression when this fraction was added to diets containing corn oil fatty acids. At the end of the experiment (14 days), the tumors of rats fed a free fatty acid diet weighed 13-17 g. The tumors of rats fed CLD, corn oil diet and the corn oil free fatty acid diet plus the NSF of corn oil weighed 1-5 g. These results indicate that something in the NSF of corn oil was associated with the regression of the tumor. However, the nature of the dietary components promoting tumor regression, and the host response to those components, have not been determined.     

牛磺酸与高脂膳对二甲基苯蒽诱发大鼠乳癌的影响

目的 :　探讨牛磺酸和 /或高脂饲料对二甲基苯蒽 ( DMBA)诱发大鼠乳腺癌的影响 ,初步探讨其可能的机制。方法 :　初断乳雌性 SD大鼠 1 0 1只 ,随机分为牛磺酸组 ( Tau)、牛磺酸 +高脂组 ( TH)、高脂组 ( HF)和对照组 ( CL) ,于 6w龄灌胃给予 DMBA后 ,分别饲以不同饲料。实验期 2 6w,实验结束时处死全部动物 ,检查肿瘤发生情况并进行血清抗氧化、血脂及免疫学指标检测。结果 :　Tau组乳腺肿瘤发生率低于 HF组而与 CL组差异未见显著性 ;平均瘤重 Tau组低于 CL组和 HF组 ;各组肿瘤平均潜伏期未见明显差异。与 CL组比较 ,Tau组血清 SOD、GSH- Px活力增高 ,LDL- C、MDA含量下降 ;HF组可见 GSH- Px活力和抗体生成能力下降 ,血清 TC升高 ;而添加了 Tau的高脂饲料组 ( TH)则仅出现了 GSH- Px活力的下降。结论 :　膳食中补充 5 %牛磺酸对诱发肿瘤的生长具有一定的抑制作用 ,并在一定程度上对抗高脂膳食的促癌作用。该作用可能是通过调节免疫功能、增强抗氧化能力及调节脂代谢等多种途径实现的     

Iron deficiency alters DMBA-induced tumor burden and natural killer cell cytotoxicity in rats.

Natural killer (NK) cell activity is impaired in iron-deficient rats. Natural killer cells destroy tumor cells; therefore, iron-deficient rats may be less able to combat cancer growth. Natural killer cell cytotoxicity, both basal and interferon gamma (IFN gamma)-stimulated, was studied in moderately and severely iron-deficient rats challenged with the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). Female weanling rats were fed ad libitum semipurified diets containing 8, 13 or 42 mg Fe/kg. A pair-fed group was fed the 42 mg Fe/kg diet at the level consumed by the 8 mg Fe/kg group. Following 6 wk of dietary treatment, DMBA-treated rats received a single intragastric dose of DMBA. Dietary treatment was continued. Rats were killed at 1, 4, 8, 14 and 20 wk post-DMBA treatment. Natural killer cell cytotoxicity (both basal and IFN gamma-stimulated) was analyzed. Feeding the 13 mg Fe/kg diet resulted in lower NK cell activity (P = 0.006) and greater tumor burden (P = 0.045) and tumor incidence. Interferon gamma treatment relieved the lower NK cell cytotoxicity observed in moderate iron deficiency. Feeding the 8 mg Fe/kg diet impaired NK cell activity (P = 0.006), but tumor burden and incidence were less than in moderate iron deficiency. In this model, iron deficiency, particularly moderate iron deficiency, contributed to cancer development and compromised NK cell cytotoxicity.     

Dietary soybean isolate and methionine supplementation affect mammary tumor progression in rats.

The effect of feeding soybean protein isolate (SBP) diet or soybean protein isolate diet supplemented with 0.7% DL-methionine (SBP + Met) on mammary tumor progression was investigated. Sprague-Dawley female rats were fed from weaning a 20% casein (CAS) diet supplemented with 0.3% DL-methionine (AIN-76) and injected via jugular vein with N-nitrosomethylurea (NMU, 40 mg/kg body weight) at 7 wk of age. Five weeks after NMU treatment, animals were divided into the three isoenergetic, isoprotein diet groups: CAS (25 rats); SBP (26 rats) and SBP + Met (25 rats). First palpable mammary tumors were evident 8, 9 and 13 wk and the mean latency period was 13.30 +/- 1.23, 16.70 +/- 1.32 and 17.82 +/- 1.28 wk after NMU treatment in the CAS, SBP + Met and SBP diet groups, respectively. Tumor incidence was 80% in the CAS group compared with 42.3% in the SBP group (P = 0.01). Methionine supplementation increased tumor incidence to 64%. Total number and total weight of tumors was greater in the CAS group compared with either SBP + Met or SBP groups: 41 vs. 28 or 21 tumors and 97.28 g vs. 27.87 or 32.46 g, respectively. These data indicate that SBP diet, low in methionine content, fed 5 wk after carcinogen exposure significantly repressed mammary tumor progression. Methionine supplementation increased the number of animals with tumors but not the mean tumor weight.     

Husband‐wife diet concordance and changes in dietary practices by surviving spouses of cancer cases

We investigated whether sodium butyrate, administered orally as gastroresistant slow‐release pellets to rats, could affect markers of colon carcinogenesis. F344 male rats were fed a high‐fat diet (230 g/kg corn oil, wt/wt) and treated with two injections (1 wk apart) of azoxymethane (15 mg/kg sc) or saline. Rats were then divided into two groups: one received the diet with 1.5% (wt/wt) sodium butyrate for 10 weeks to provide 150 mg butyrate/day, and one group received no butyrate. At the end of this period, rats were sacrificed, and colonic proliferative activity, number of aberrant crypt foci (ACF), and apoptosis were assessed in the colon. The proliferative activity and A CF induction were not affected by butyrate pellet administration. On the contrary, in rats treated with butyrate, apoptotic index increased from 0.12 ± 0.12 to 0.81 ± 0.10 (means ± SE, p < 0.05). The short‐chain fatty acid concentration was significantly increased in the feces of rats treated with butyrate. In conclusion, the increase in the mucosal apoptotic index suggests that gastroresistant butyrate pellets have a beneficial effect against colon carcinogenesis. However, because butyrate pellets did not modify proliferation or ACF induction, this conclusion should be confirmed in long‐term carcinogenesis experiments.     

Uptake and Metabolism of Hydroxymatairesinol in Relation to Its Anticarcinogenicity in DMBA-Induced Rat Mammary Carcinoma Model

The chemopreventive effects of hydroxymatairesinol (HMR), a lignan extracted from Norway spruce (Picea abies), on the development of mammary carcinoma induced by 7,12-dimethylbenz[a]anthracene (DMBA) was studied in rats. HMR administered via diet in an average daily dose of 4.7 mg/kg body wt starting before DMBA induction reduced tumor volume and tumor growth, but no significant reduction in tumor multiplicity (number of tumors/rat) was observed. The predominant histological type in the control group was type B (well-differentiated adenocarcinoma, 78%). The proportion of type B tumors decreased to 35% in the HMR group, while the type A (poorly differentiated) and type C (atrophic) tumor proportions increased. Anticarcinogenic effects of dietary HMR (4.7 mg/kg) were also evident when the administration started after DMBA induction and was seen as growth inhibition of established tumors. Dietary HMR supplementation significantly increased serum and urinary enterolactone and HMR concentrations but had no significant effect on the uterine weight, suggesting that HMR or its major metabolite enterolactone did not have an antiestrogenic effect. Further studies are warranted to further clarify and verify HMR action and the associated mechanisms in mammary tumorigenesis.     

Adaptation of lingual lipase to dietary fat in rats

To study the adaptive response of lingual lipase and pancreatic lipase to dietary fat, three sets of experiments were performed in adult male rats. In the first experiment, rats were fed for 3 wk a low fat diet (4.5% fat) or a 10, 20 or 30% fat diet. In the second, rats were fed a 4.5% fat diet for 4 wk or a 20% fat diet for 1, 2 or 4 wk. In the third, rats were fed for 3 wk a 10% fat diet with various sources of fat (lard, sunflower oil, olive oil, peanut oil, butter, soybean oil, corn oil or salmon oil). The results demonstrated that 10% dietary fat was sufficient to promote a maximum significant increase in lingual lipase activity (expressed in units/g tissue and in units/mg protein), whereas pancreatic lipase responded steadily to 20 and 30% fat diets. After 1 wk of feeding 20% dietary fat, both enzyme specific activities had reached their maximum values. The fatty acid composition of dietary triglyceride molecules (chain length, number and location of double bonds) had no specific effect on the adaptation of lingual lipase. The physiological implications of these findings are discussed in regard to the role of intragastric lipolysis in fat digestion.