Search

Groups of 40 Syrian golden hamsters of both sexes were fed diets containing either 5% fat (control), 20% saturated fat (beef tallow) or 20% unsaturated fat (sunflower seed oil) from weaning and during the whole experimental period (up to 656 days). Respiratory tract tumours were induced by intratracheal instillation of benzo[a]pyrene attached to ferric oxide and suspended in saline. Mortality was slightly, but not statistically significantly higher in the high fat groups than in the low fat control group. Microscopic examination of the respiratory tract revealed an increased number of tumour bearing animals, an increased multiplicity of respiratory tract tumours and an increased total number of respiratory tract tumours in animals fed high fat diets. The tumour enhancing effect of fat was most pronounced in the high unsaturated fat group. Especially epidermoid papillomas, epidermoid carcinomas and combined epidermoid and adenocarcinomas contributed to the observed differences in tumour response amongst groups. It was concluded that dietary fat enhances benzo[a]pyrene-induced respiratory tract carcinogenesis in hamsters.

The effects of vitamins A, C and E on the development of putative preneoplastic foci in exocrine pancreas were investigated in azaserine-treated rats and N-nitrosobis(2-oxoproypy)amine-treated hamsters. The animals were fed a semipurified diet high in saturated fat (20% lard) either or not supplemented with vitamin A, vitamin C or vitamin E. A separate group maintained on a diet low in saturated fat (5% lard) was incorporated as extra controls. The animals were given their diets 12 days after the last treatment with carcinogen. At 4 months postinitiation, the pancreata were quantitatively examined for both the number and size of early, putative preneoplastic lesions and the presence of neoplastic lesions. Rats as well as hamsters maintained on 5% lard exhibited a significantly lower number of putative preneoplastic pancreatic lesions than animals fed a diet containing 20% lard. Growth of acidophilic but not of basophilic foci was inhibited in rats of the high vitamin A and C group, whereas vitamin E exerted an inhibitory effect on growth of basophilic but not of acidophilic foci. In hamsters maintained on a diet high in vitamins A or C, the number of early ductular lesions was significantly decreased, whereas the number of (micro)carcinomas was increased. Vitamin E did not have any modulating effect on development of ductal lesions in hamster pancreas.

The promoting effect of dietary corn oil (CO), safflower oil (SO), olive oil (OO), coconut oil (CC), and medium-chain triglycerides (MCT) on azoxymethane (AOM)-induced colon tumors was studied in female F344 rats. The animals were fed low-fat diets containing 5% CO, 5% SO, or 5% OO 2 weeks before, during, and 1 week after sc injection of 20 mg AOM/kg body weight. One week after the AOM treatment, groups of animals were transferred to high-fat diets containing 23.52% CO, 23.52% SO, 23.52% OO, and 23.52% CC, or 5.88% CO + 17.64% MCT; the remaining animals were continued on 5% fat diets. All animals were fed these diets until the termination of the experiment. Body weights and intakes of calories, protein, and micronutrients were comparable among the various dietary groups. The incidence of colon tumors was increased in rats fed diets containing high-CO and high-SO compared to those fed low-CO and low-SO diets, whereas the diets containing high OO, CC, or MCT had no promoting effect on colon tumor incidence. There was a significant increase in the excretion of fecal deoxycholic acid, lithocholic acid, and 12-ketolithocholic acid in animals fed the high-CO and high-SO diets and no difference in these secondary bile acids excretion in animals fed the high-OO and high-CC diets compared to those animals fed their respective 5% fat diets. This study thus indicates that not only the amount of dietary fat but also the fatty acid composition (type) of fat are important factors in the determination of the promoting effect in colon carcinogenesis.

Numerous studies have reported a positive relationship between dietary fat and chemically induced tumor incidence. The results of the 2-year carcinogenesis bioassay used by the National Toxicology Program (NTP), in which test compounds were administered to rodents by corn oil gavage, provide an opportunity to compare the effects of fat on chemically induced and naturally occurring tumors. Oil gavage increases the fat intake about threefold, equivalent to a 15% fat diet. Only 2 oil gavage effects were observed in the NTP carcinogenesis bioassay. First, pancreatic hyperplasia was increased from 2.6% in untreated controls to 12.6% in male Fischer 344/N vehicle control rats; however, this sporadic and weak effect did not influence the outcome of carcinogenesis bioassays. Second, leukemia/lymphoma incidence was about 50% lower in male vehicle controls than in the untreated control rats; in contrast, this strong effect increased survival by 8-10%. Therefore, oil gavage had an apparent protective effect in male Fischer 344/N rats. The absence of growth enhancement for the relatively high background level of tumors in oil gavage-treated rats was remarkable and is inconsistent with observations in rat mammary tumor model studies. Because it is impossible to extrapolate the enhancing effect of a high fat diet on tumor growth from rodent tumor models to the NTP carcinogenesis bioassay, great caution should be used in extrapolating from rodent tumor model studies to the human situation.

Four groups of weanling rats were fed semisynthetic diets containing 15 percent by weight of dietary fats for 28 days. Two groups received thermally oxidized low-erucic acid rapeseed oil (OLE) or lard (OLA) and the other two groups received the respective fresh fats (FLE, FLA) as controls. Average daily feed consumption and feed efficiency were not affected by either OLE or OLA, however final body weights were depressed by the OLA in the diet. The relative heart weights and heart total lipids were significantly increased in both the OLE and OLA groups. A majority of the animals in both the OLE and OLA groups exhibited various gross symptoms attributable to heated fat toxicity such as seborrhea, diarrhea and polyuria. Excessive hair loss was noted in all the animals fed the heated fats. Tissue fatty acid changes due to OLA were confined largely to the polar liver lipids, whereas OLE produced dramatic changes in both the neutral heart lipids as well as in the neutral and polar liver lipids. Histological evaluation of the hearts, livers and kidneys indicated that OLA was very injurious to the kidneys, whereas OLE caused greater damage to both the hearts and livers.

Commercial hydrogenation of vegetable oils results in the introduction of trans fatty acids. In the present study, we have investigated the effect of feeding a fat which contained approximately 38% trans isomers (designated trans fat) on the induction of mammary tumors by dimethylbenz(a)anthracene in rats. The corresponding control fat (designated cis fat), which had a similar fatty acid composition, consisted of only cis isomers. Since both the trans and cis fats were rather saturated, a comparison was also made between these 2 types of fat and corn oil, which contains about 60% linoleic acid (C18:2). Each fat was present in the diet at 2 levels, 5 and 20% by weight. Although rats fed the 20% trans fat or cis fat diets had a slightly higher tumor incidence and yield than did those on the corresponding 5% fat control diets, the difference was not statistically significant. In contrast, rats fed the 20% corn oil diet developed a much greater number of tumors than did rats fed a diet containing only 5% corn oil. Further analysis of the data showed that diets containing either trans fat or cis fat were much less effective than were the corn oil diets in promoting the development of mammary neoplasia at either the 5 or 20% level. Our results thus suggest that trans fat behaves very much like a saturated fat in the modification of mammary tumorigenesis. A determination of the fatty acid content of the mammary fat pad indicated that its composition generally reflected the dietary fatty acid intake, with the incorporation of trans isomers into the mammary tissue found to be dependent on the quantity of trans fat in the diet.

Five groups of male weanling rats were provided purified diets containing 15% by weight of either fresh or laboratory-heated corn oil (FCO, HCO) or fresh, laboratory-heated, or commercial pressure deep-fry peanut oil (FPO, HPO, PPO). Total weight gain, feed consumption, and feed efficiency were consistently greater for the FCO, FPO, and PPO groups. Although relative heart weights were unaffected, the HCO and HPO produced elevated liver and kidney weights. The dietary fats had no effect on the hematological status of the animals or the proportions of cells comprising the total leukocytes of the blood. Physical, chemical, and microscopic evaluation of the urine detected no pathologic conditions. Rats fed diets containing HCO or HPO demonstrated toxicity of thermally oxidized fats by the appearance of diarrhea, dermatitis, seborrhea, and hair loss. Histological examinations revealed injury of the thymus by all fat samples except the FCO; the liver was damaged by the HCO, HPO, and PPO, and the testes and epididymides by HPO and PPO. In the latter case there was complete cessation of spermatogenesis.

C57BL/6J mice were given a gavage of from 0.1 to 0.4 ml beef tallow (BT) or corn oil (CO). The damaging effect of the orally administered fat boluses could be visualized 2-4 h later by instilling the excised animal colons with Trypan blue, a vital dye that stains non-viable cells. Microscopic examination of sections prepared at these times revealed that the tall columnar cells on the surface of the normal epithelium were replaced with cells demonstrating flattened, pleomorphic, pyknotic and fragmented nuclei. This phenomenon was quantitated by scoring 100 intercrypt epithelial zones between well-defined crypts. The maximum damage, affecting 25-45% of the epithelial zones, was seen at 2-4 h after treatment with 0.4 ml of BT or CO and the epithelium appeared normal with less than 10% damage at 12 h. The mitotic activity in the colonic crypts was unchanged up to 8 h and then showed a marked increase of 2- to 3-fold at 12-16 h. The severity of the epithelial damage and ensuing mitogenic response was related to the size of the fat bolus. These observations would suggest that the effects of any carcinogens present in the diet or formed in the feces could be enhanced if a fatty meal results in colonic damage and subsequent cell proliferation as we have observed in mice.

Six cooking oils with different levels of unsaturation were each heated at 180 +/- 3 degrees C for 6 hr on each of four consecutive days and cut potatoes were fried in the oils at hourly intervals. Samples of the heated and unheated oils were tested in the Ames mutagenicity assay. None of the oil samples (taken before or after 24 hr heating) showed any mutagenicity in the Ames test with or without metabolic activation.

Male Sprague-Dawley rats were fed semisynthetic diets containing 25% (w/w) experimental lipid. A partially hydrogenated herring oil (PHHO), containing 25% C22:1 as an isomeric mixture dominated by cetoleic (cis-docos-11-enoic), but partially altered to the trans form and containing other positional isomers, was compared with lard:corn oil 3:1(LCO) (w/w). The feeding period extended up to 111 weeks. Ten animals from both groups each were sacrificed at 2, 8, 16, 24, and 32 weeks. The remaining animals from each group were kept on the diets either until spontaneous death occurred or until Week 111. The LCO rats had higher serum cholesterol levels. The PHHO rats had transient myocardial lipidosis and very severe, progressive myocardial inflammation and scarring.

The possible toxicity and mutagenicity of a heated liquid fraction derived from palm oil by transesterification was tested with rats fed diets containing 15% of the oil and by various in vitro and chemical assays on the animals sera. No adverse effects of any kind were noted in the animals fed diets containing a high level of the oils, and the Ames Test failed to reveal a mutagenic potential in any of them. The chemical tests did not show any noteworthy undesirable changes, either.

High linoleic acid (C18:2) (group I; 17.7 cal%) and low C18:2 (group II; 3.3 cal%) diets were given to groups of inbred Brown Norway virgin female rats (100 animals/group), during their whole life-span. A total of 140 tumors were found in group I and 123 tumors in group II; the median survival times of the 2 groups were 124.2 and 118.5 weeks, respectively. Total spontaneous tumor incidence and median survival times were not significantly different. However, significant differences were found in the incidences of some specific tumors: The numbers of reticuloendothelial tumors and adrenocortical carcinomas were significantly higher in the group of animals receiving the low-C18:2 diet. A high incidence of tumor multiplicity, however, resulted in a significantly greater number of mammary tumors in the high-C18:2 diet group.

Weanling male Sprague-Dawley rats were fed diets containing 20% by weight corn, soybean or low erucic acid rapeseed oils or mixtures of the latter two with cocoa butter or triolein for 1, 2, 3 or 4 weeks. These diets previously had been fed to the same strain of rats for 16 weeks, and a reduction in the incidence of focal heart lesions had been observed with the addition of cocoa butter, but not triolein. The cardiac lipid classes and the fatty acid and alkenyl ethers of the cardiac phospholipids were analyzed to determine if changes could be attributed to the observed cardiopathological response, and at what time. Cardiac lipid classes changed during post-weaning development, but only triacylglycerol was diet-related. A number of fatty acid changes were observed in the cardiac phospholipids which reflected the relative concentration of saturates, monounsaturates, linoleic acid and linolenic acid in the diet, but only the changes in saturates and the C22 polyunsaturated fatty acids from the linolenic acid family appeared to be related to the incidence of focal heart lesions. Arachidonic acid and the total C22 polyunsaturated fatty acids remained fairly constant throughout the feeding trial. Cardiac diphosphatidylglycerol was least affected by dietary manipulation, while nervonic acid increased in cardiac sphingomyelin when small amounts of erucic acid were present in the diet. Fatty acid changes were essentially completed after one week on the experimental diets, whereas changes in the alkenyl ethers took two to three weeks.

Used frying oil can be separated by means of column chromatography on silica gel into an unpolar fraction, which contains predominantly the unaltered triglycerides, and a polar fraction consisting of all oxidation and decomposition products formed during the heating process. The size of the polar fraction indicates the degree of fat deterioration. A similar procedure was applied to obtain fractions from a heated oil to be used in long-term feeding experiments. Several tons of a sunflower oil which had been used in the industrial production of fish fingers were separated into a polar fraction (1) and an unpolar fraction (2). The sunflower oil had not been overheated and was taken at the moment when the production would have been stopped, according to factory practice, and the oil discarded. Fractions 1 (group U) and fraction 2 (group P) as well as the original unheated sunflower oil (group F) and the heated sunflower oil (group H) were fed to rats over 18 months at a level of 20% in the diet. Fraction 1 caused a highly significant reduction in weight gain of the animals as compared with unheated sunflower oil but had only an insignificant detrimental effect upon the many biochemical, histological and clinical parameters. The order of the weight gain caused by the four samples was: U < H < P < F. The changes of other parameters as well as the implications of these long-term feeding studies will be discussed in detail.

The effects of coffee and dietary fat (alone and in combination) on the development of preneoplastic lesions in exocrine pancreas were investigated in rats and hamsters, treated with azaserine or N-nitrosobis(2-oxopropyl)amine, respectively. The animals were given the respective diets (5% or 25% corn oil) and coffee (instead of drinking water) within one week after the treatment with carcinogen. At four months postinitiation, the pancreata were quantitatively examined for the number and size of preneoplastic foci. In rats, coffee alone inhibited growth of acidophilic foci and, moreover, slightly inhibited the positive modulating effect of fat on growth of these foci, pointing to a negative rather than a positive interaction between these two life-style factors. In hamsters, coffee alone enhanced growth of cystic foci, whereas fat alone enhanced growth of ductular foci. An interaction between fat and coffee on pancreatic carcinogenesis in hamsters could not be demonstrated.

Dietary corn oil was consumed by Syrian golden hamsters at levels of 4.5 g [low fat (LF)] or 18 g [high fat (HF)]/385 kilocalories (kcal) from 3 to 7 weeks of age followed by a diet containing 9 g [medium fat (MF)]/385 kcal for life. In other groups MF diet was given from 3 to 7 weeks of age and followed by either LF or HF for life. A separate group was fed MF continuously after 3 weeks of age. Spontaneous lesions, which were altered by these dietary protocols, are reported. An HF diet fed after 8 weeks increased the incidence of flank organ hyperplasia and prostatitis, but it decreased prostatic fibrosis in males. Consumption of HF diets after 8 weeks by females increased survival and resulted in an elevated incidence of thyroid adenomas, ovarian cell hyperplasia, vaginal papillomas, and adrenal cortical cell adenomas. In age-adjusted data the increase in ovarian cell hyperplasia and adrenal cortical cell adenomas was shown to be due to HF diet and not to be a consequence of extended survival. Periodontitis and calcification of cardiac tissues decreased in hamsters fed HF diets after 8 weeks, but cell vacuolization and hyperplasia of the anterior pituitary gland and epithelial hyperplasia in the forestomach were increased. Salivary gland adenocarcinomas were observed only in hamsters fed HF diets. Feeding HF levels, either during weeks 3-7 or after week 8, decreased osteofibrosis and otitis media and increased urinary bladder epithelial hyperplasia, adrenal cortical cell lipomatosis, and bone chondrosis. Calcification of gastric and renal arteries decreased as dietary fat levels increased either before or after 8 weeks of age in males and only when fed after 8 weeks in females. Colitis and focal glandular hyperplasia of the colon mucosa were increased in both sexes by an HF diet being given before or after 8 weeks of age.

The effects of dietary soybean oil (SBO) concentration (5 vs. 20% by weight) on mammary tumorigenesis, mitogen-induced blastogenesis, cell-mediated cytotoxicity and serum and lymphocyte fatty acid composition were studied in C3H/OUJ female mice. Weanling mice fed 20% SBO for 9 mo had a higher incidence (89 vs. 65%) and greater average size (2.9 vs. 1.9 g) of mammary tumor virus type S breast tumors than mice fed 5% SBO. The response of isolated splenocytes to the T-cell mitogens concanavalin A and phytohemagglutinin was 20-25% lower in mice fed 20% SBO than in mice fed 5% SBO for 20 wk. There was no effect of SBO concentration on the splenocyte response to lipopolysaccharide E55:B5, a B-cell mitogen, or to pokeweed mitogen, and B- and T-cell mitogen. Cell-mediated cytotoxicity to allogenic P815 tumor cells was 20% lower in mice fed 20% SBO than in mice fed 5% SBO for 12 wk. The lower cell-mediated immunity associated with 20% SBO was not due to changes in the fatty acid composition of the two major splenocyte membrane phospholipids, phosphatidylcholine and phosphatidylethanolamine. However, serum levels of linoleic acid were higher in mice fed 20% SBO. Raising dietary SBO from 5 to 20% by weight was associated with increased mammary tumorigenesis, reduced T-cell blastogenesis and lower cell-mediated cytotoxicity.

Rabbits were fed diets enriched with cholestanol or cholesterol (3.5 g/wk) for 4-12 weeks. During cholestanol feeding, the concentration of cholestanol in blood serum, liver, heart and aorta increased 15-30 times. In serum and liver, the concentration of cholesterol also increased. Cholestanol-fed rabbits developed inflammatory changes in the liver, with proliferation of small bile ducts. Liver tests were only slightly abnormal. Morphological atherosclerosis of the aorta was only occasionally seen in rabbits receiving cholestanol for eight weeks or less. During cholesterol feeding, the amounts of cholesterol in different tissues increased dramatically, most in the aorta. Morphological atherosclerosis in the aorta was found in all rabbits fed cholesterol-enriched diets for more than four weeks. Brain cholestanol was doubled in rabbits fed cholestanol for eight weeks, whereas brain sterols did not change significantly during cholesterol feeding. After an additional regression period with cholestyramine for eight weeks, the increased content of cholestanol in the brain was unchanged in cholestanol-fed rabbits. These observations are discussed in relation to the cholestanolosis of the brain that develops in the rare inherited human disease cerebrotendinous xanthomatosis.

A high-performance liquid chromatography procedure was developed to measure linoleic acid hydroperoxides (LAHPO) in 19 used, deep-frying fat samples that were screened for mutagenicity. The detection limit of the method was found to be 10 nmol of LAHPO/g of fat. In eight samples, LAHPO were not detected; levels in the other samples ranged from 17 to 267 nmol/g of fat. LAHPO were not detectable in unused hydrogenated frying fat samples. Concentrations of LAHPO correlated positively with mutagenicity to Salmonella tester strains TA97 and TA100, in presence of S9 mix only; coefficients of correlation were, respectively, r=0.48 (p less than 0.05) and r=0.24 (n.s.). Without metabolic activation no significant associations or secondary autoxidation products of linoleic acid generated in presence of liver S9 mix may contribute to mutagenicity of some of the used deep-frying fat samples.

Serum and liver tissue fatty acid and lipid fraction values were studied in rats kept for various periods on a hyperlipid, hypoprotein, steatogenous diet, with or witout choline. There was a general increase in liver fats due to an absolute increase in triglycerides, accompanied by changes in the fatty acid methyl ester composition, indicating the storage of lipids of lesser metabolic activity and more similar to those of peripheral fat (palmitic and oleic acid increments; decreases in myristic, stearic, linoleic and arachidonic acid values). These changes were partly reflected in the blood picture: little difference in lipid fraction ratios, coupled with fatty acid gas chromatograms similar to those observed for the liver. The omission of choline aggravated the alterations caused by the experimental diet.

Albino rats were kept for long periods on a steatogenous, hypoproteic, hyperlipidic diets, either with or without choline. Serum protein and liver soluble protein and enzyme values showed changes that were only partly similar to those observed in human and experimental cirrhosis. The main features, in fact, were an absolute and percent decrease in albumins, an increase in serum alpha1-globulins and alpha proteins generally, and, more particularly, a constant fall in gamma-globulins and enzymes migrating to this site.