No description available.

This study was designed to determine the distribution of fatty acids and cholesterol in total tumor and mammary tissues. Fatty acid profiles of phospholipid fractions from tumors and mammary glands were also determined. Fatty acids and cholesterols were analyzed by gas liquid chromatography. Methodology was developed for phospholipid separation by high performance liquid chromatography.Tumors derived from mammary glands in Strain A/ST mice were found to contain two to three times the amount of cholesterol compared to normal mammary glands. Mammary glands from safflower fed mice contained significantly higher percentages of linoleic acid. Linoleic acid content in stearicacid (SA-1) fed mice was sharply reduced. linoleic acid in mammary glands of animals fed a high fat Stearic acid (SA-4) , corn oil and stock diet fed animals displayed similar fatty acid profiles. Fatty acid analysis of tumors excised from mice fed the experimental diets showed similar patterns in comparison to normal mammary glands. The similar distributions were in the 18 carbon fatty acids. Distributions of phospholipid fatty acids in tumors and mammary glands were similar. Mammary gland phospholipids displayed increased percentages of short chain (14 carbons and under) fatty acids. Results of these studies demonstrate an increased availability of diet rich in polyunsaturated fatty acids.

In an effort to determine the metabolic changes that occur in fatty acid oxidation during the rapid growth period, the activity of carnitine palmitoyltransferase was measured in four groups of animals at 4, 8, 12 and 16 weeks of age.Muscle samples were taken from the soleus after animals were anesthesi2ed, and the samples were assayed for CPT activity. The CPT activity was significantly higher at 4 weeks than at 8, 12 and 16 weeks (p0.0001), and the fl week activity was significantly higher that the 16 week animals. It was found that there were two distinct phases of decline in CPT activity. The first occured from 4-8 weeks where a 74% drop in activity was recorded. The second phase was a more gradual decline that occured after 8 weeks. 21% decline in activity occured between 8 and 12 weeks, followed by a 23% decrease after 12 weeks. The first drastic drop in activity can be attributed to the residual heightened enzyme concentration carried over from the suckling period in which the rat was exposed to a high fat diet found in the mother's milk. The second phase of the decline in activity is due to a dietary change which caused a shift in metabolism from fat to glucose as the primary carbon source for fuel. / School of Physical Education

Phospholipase C mediated hydrolysis of the phosphoinositides yields second messenger products which have been linked to normal and abnormal cell growth processes. It has been suggested that fatty acids may regulate phospholipase C activity in vivo. This study sought to investigate relationships between phospholipase C activity, tumor size and dietary linoleic and stearic acids.Phospholipase C activity, of livers and serially transplanted mammary adenocarcinomas from female strain A/ST mice on one of three diets, was measured. Tumors ranged from .20 to 2.98 g at the time of removal. Phospholipase C activity of tumors was negatively and significantly (p<.Ol) correlated to increasing tumor weight in those diet groups that contained linoleic acid and no added stearic acid. The highest PLC activity was seen in small tumors across all diet groups. Maximum PLC activity of tumors was over 2 fold higher than the maximum activity of livers across all diet groups. PLC activity of the liver was negatively and significantly (p<.02) correlated to increasing tumor weight for samples from the high linoleic acid diet (SF-15). This research concludes that PLC activity varies during tumorigenesis and may reflect tumor development. / Department of Biology

Cyclopropene fatty acids (CPFA) found in cottonseed oil (CT) have been shown to reduce production of progesterone, a precursor of estrogen. Estrogenic hormones have been implicated in enhancing growth of mammary tumors. In this study, the effect of dietary cottonseed oil on estrogen production by mature female mice was determined by measuring urinary estrogen using High Performance Liquid Chromatography.At four months of age, five groups of three Strain A/ST female mice were placed on 20% fat diets containing 0, 2.5, 5.0, 10, and 20% cottonseed oil. The remainder of the fat in the experimental diets was corn oil sufficient to provide the balance of the 20% fat content in conjunction with other nutrients of equal percentages in all diets. At five day intervals mice were housed in metabolic cages and twenty-four hour urine samples were collected. Urine was purified on C18 columns and eluted with 1% phosphoric acid: acetonitrile: methanol: (54:35:11). Estrogen was quantified by High Performance Liquid Chromatography using a 250 X 5mm C18 column, hydrocortisone as an internal standard, and variable wavelength recorder set at 242 nm. The level of urinary estrogens after day 35 of the study was lower in all diets containing cottonseed oil. This is in agreement with several authors who have reported instances of physiological abnormalities in mammals which were fed increasing but low levels of dietary cyclopropenes. Since elevated estrogen levels have been identified as a risk for breast cancer, this study examines the relationship between dietary cyclopropenes and estrogen hormone production in strain A/St mice. / Department of Biology

To investigate the possible changes in pyruvate oxidation during the rapid growth period in an animal model, the oxidation of radioactive labeled pyruvate was measured in mitochondria isolated from the gastrocnemius muscle of Sprague--Dawley rats between 4 and 16 weeks of age. The influence of the fatty acid derivative palmitylcarnitine, as an inhibitor of pyruvate oxidation, was also tested.The gastrocnemius muscle was removed from anesthesized animals at 4, 8 and 16 weeks of age. Isolated mitochondria from the muscle samples were incubated with C1--14C] pyruvate and E1-14C] pyruvate + palmitylcarnitine in a KC1 medium. The decarboxylation of pyruvate was measured by the evolution of radioactive labeled carbon dioxide. Pyruvate oxidation significantly (p .; 0.0001) increased from ages 4 to 16 weeks. The initial low rate of pyruvate oxidation was attributed to the residual metabolic effects of the pre-weaned animal' high-fat diet. The subsequent increase in the capacity of pyruvate oxidation was then explained by the shift in the animaldiet to high-carbohydrate lab chow. These results may also be attributed to the maturation of the hindlimb muscle fibers during this period: the differentiation of predominately red, oxidative fibers to an increase in the percentage of white, glycolytic fibers, common in the adult hindlimb. The fatty acid derivative, palmitylcarnitine, failed to inhibitpyruvate oxidation at the level of decarboxylation. This finding supports the proposal that fatty acids do not inhibit glucose oxidation directly, but instead suppress glycogen breakdown. Thus, the findings indicate an increase in the capacity for- pyruvate oxidation during the rapid growth period without inhibition by the fatty acid derivative, palmitylc_arnitine. / Department of Biology

Penicillium chrysogenum was investigated to determine whether there are lipoproteins specifically associated with fatty acid synthesis and in what fraction of P. chrysogenum they are located. Radio-activity labeled free fatty acids and CoA thioester substrates were added to cell-free extracts and incubated. Samples of these incubation mixtures were analyzed for lipoprotein content with electrophoresis and for the presence of radioactivity with a radiochromatogram scanner and scintillation spectrometer.Label from fatty acyl thioester substrates migrated with protein fractions having alpha-2 or beta mobility showing the existence of lipoproteins associated with fatty acid metabolism in cell-free extracts of P. chryogenum. The percent distribution of radioactivity from the thioester incubations supported previous work in this laboratory on the desaturase system and suggested the presence of a long chain fatty acyl-CoA-ACP synthetase enzyme in Penicillium chrysogeum.

Dietary linoleate enhances the development of mammary tumors while dietary stearate has a retarding effect. Since linoleate is a precursor of prostaglandin E2 and elevated levels of prostaglandin E2 have been shown to be associated with tumor development, levels of dietary linoleate directly influence the levels of prostaglandin E2 available for tumor development. The development of new tumor tissue also involves a high demand for fatty acids to be incorporated into cell membranes and this demand is for specific types of fatty acids to maintain the required membrane fluidity.Several enzymes play key roles in the synthesis and desaturation of the fatty acids which are converted to prostaglandins and are synthesized for membrane incorporation. Among these are fatty acid synthetase and linoloeyl coenzyme A desaturase. This study examined the activity of these two enzymes in liver tissue of mice maintained on test diets containing varying proportions of the fatty acids stearate and linoleate.Animals fed a high fat (15% of total) diet containing 13.1% stearate were found to have higher linoloeyl coenzyme A deeaturaae activity than animals fed a low fat diet or a high fat diet containing 11.3% linoleate diets. Animals fed the high fat, high stearate diet were found to have a higher fatty acid synthetase activity than animals fed either a low fat diet or the high fat, high linoleate diet.

Dietary fatty acids are considered promoters of murine and human mammary tumors. The mechanism responsible is not known. Mammary adenocarcinomas in mice originate from preneoplastic cells (hyperplastic alveolar nodules (HAN)) which are derived from normal mammary epithelial cells. Diets rich in linoleic acid (18:2) have been associated with increased incidence of HAN and promotion of tumor growth. Diets rich in stearic acid (18:0) have been associated with decreased incidence of HAN and increased latency period for mammary tumor formation in mice.The effects of dietary 18:0 and 18:2 stages of murine mammary tumorigenesis were examined. The purpose of this study was to determine the effects of these dietary fatty acids on HAN production, mammary gland development, and fatty acid composition of mammary epithelial cells and adipocytes.Spontaneous mammary tumor producing strain A/ST mice were fed a high fat (15%) or low fat (5%) diet. High fat stock (ST) diet containing 1.5% 18:2 or a low fat corn oil (CO) diet containing 3% 18:2 were fed. Animals were sacrificed at 6 or 10 months of age. HAN, ductile and alveolar development were histologically determined in the left inguinal mammary gland. The contralateral gland was on the early diets rich in 18:2 (SF) or 18:0 (SA) were fed. A low*fat enzymatically dissociated and fatty acid compositions of adipocyte and epithelial cells were determined by GLC. Fatty acid profiles were examined for correlation to histologic findings.SA-fed mice had fewer HAN and less well developed mammary alveoli than the other dietary groups which exhibited moderate (ST) or high (CO, SF) HAN incidence. SF-fed mice had the earliest onset of any dietary group. CO-fed mice had later onset of HAN as compared to SF-fed mice but the HAN incidence was similarly high in both groups at 10 months of age.SA-fed mice were protected from development of expected numbers of HAN as compared to ST-fed mice. The reduction in HAN risk in this group was associated with reduced mammary alveolar development. Groups with high risk of HAN (SF and CO) exhibited increased amounts of 18:2 in their mammary epithelial cells and adipocytes. / Department of Biology

The purpose of this research was to determine the effects of adding alternate carbon sources to a ten percent glucose or sucrose medium on growth, fatty acid distribution, and incorporation of radioactive carbon sources into lipids using submerged Aspergillus niger cultures.